Our latest articles are presented here.

A complete list of publications can be found at the bottom of this page.

European Journal of Pharmaceutics and Biopharmaceutics (2023)

Plasma membrane depolarization reveals endosomal escape incapacity of cell-penetrating peptides

Marc Serulla, Palapuravan Anees, Ali Hallaj, Evgeniya Trofimenko, Tara Kalia, Yamuna Krishnan, Christian Widmann

The capacity of cell-penetrating peptides (CPPs) to escape endosomes is a debated issue (check our movie out on youtube). In the present paper, we monitored endosomal escape in conditions where cells were allowed to take up CPPs by endocytosis but not by direct translocation. In these conditions no endosomal escape could be detected even when we used CPPs supposedely designed for enhanced endosomal escape capacities. This indicates that CPPs are unable to escape endosomes in significant means. What was interpreted as endosomal escape in a number of earlier publications was thus most likely corresponding to CPP cytosolic uptake by direct translocation. CPP uptake by endocytosis occurs at lower CPP concentrations than those allowing direct translocation. In a number of conditions, endocytosis might thus be the predominant mode of entry for CPPs. Endocytosis of CPP is however a dead end for them. This is why we are currently trying to identify molecules able to favor CPP endosomal escape. These “escape promoting molecules” would increase the bioavailability and activity of CPPs and consequently their usefulness in biology and medicine.

eLife (2021)

Genetic, cellular, and structural characterization of the membrane potential-dependent cell-penetrating peptide translocation pore

Evgeniya Trofimenko, Gianvito Grasso, Mathieu Heulot, Nadja Chevalier, Marco Deriu, Gilles Dubuis, Yoan Arribat, Marc Serulla, Sébastien Michel, Gil Vantomme, Florine Ory, Linh Chi Dam, Julien Puyal, Francesca Amati, Anitha Lüthi, Andrea Danani, and Christian Widmann

The mechanisms allowing CPPs to enter cells are ill-defined. Using a CRISPR/Cas9-based screening, we discovered that KCNQ5, KCNN4, and KCNK5 potassium channels positively modulate cationic CPP direct translocation into cells by decreasing the transmembrane potential (Vm). These findings provide the first unbiased genetic validation of the role of Vm in CPP translocation in cells. In silico modeling and live cell experiments indicate that CPPs, by bringing positive charges on the outer surface of the plasma membrane, decrease the Vm to very low values (–150 mV or less), a situation we have coined megapolarization that then triggers formation of water pores used by CPPs to enter cells. Megapolarization lowers the free energy barrier associated with CPP membrane translocation. Using dyes of varying dimensions in CPP co-entry experiments, the diameter of the water pores in living cells was estimated to be 2 (–5) nm, in accordance with the structural characteristics of the pores predicted by in silico modeling. Pharmacological manipulation to lower transmembrane potential boosted CPP cellular internalization in zebrafish and mouse models. Besides identifying the first proteins that regulate CPP translocation, this work characterized key mechanistic steps used by CPPs to cross cellular membranes. This opens the ground for strategies aimed at improving the ability of cells to capture CPP-linked cargos in vitro and in vivo.

This image shows a CPP (in yellow) moving across the plasma membrane through a water pore (copper structure)

Cell Reports (2021)

The endocytic pathway taken by cationic substances requires Rab14 but not Rab5 and Rab7

Evgeniya Trofimenko, Yuta Homma, Mitsunori Fukuda, and Christian Widmann

This work reports the characterization of an endocytic pathway that had escaped detection so far. In contrast to classical endocytic pathways that rely on the Rab5 and Rab7 proteins to move endocytosed material, such as transferrin, dextran, or EGF, to LAMP1-positive lysosomes, the newly described pathway move cationic substances (CPPs and polyamines for example) to LAMP1-positive compartments in a Rab14-dependent but Rab5/7-independent manner. The initial process of vesicle formation in the Rab14 pathway also differs from classical endocytosis as it is not inhibited by dynamin inhibition, macropinocytosis inhibitors, or pan-PI3K inhibitors. Even though both classical endocytic pathways and the Rab14-dependent pathway end up in LAMP1-positive vesicles, the LAMP1-containing vesicles of classical pathways are acidic and correspond to lysosomes while the LAMP1-positive compartment in the Rab14 pathway are non- acidic (or less acidic) and presumably fulfil non-degradative functions.

Comparison between the Rab5/7- and Rab14-dependent endocytic pathways. Watch the movie.

iScience (2021)

Bacterial surface properties influence the activity of the TAT-RasGAP317-326 antimicrobial peptide

Maria Georgieva, Tytti Heinonen, Alessandra Vitale, Simone Hargraves, Senka Causevic, Trestan Pillonel, Leo Eberl, Christian Widmann and Nicolas Jacquier (last two authors share senior authorship)

This study investigated the parameters that influence the binding and activity of TAT-RasGAP317-326 on bacteria. This study provides the basis for future investigation on the mode of action of TAT-RasGAP317-326, which may help developing antimicrobial treat-
ments based on this peptide

PNAS (2020)

TAT-RasGAP317-326 kills cells by targeting inner-leaflet-enriched phospholipids

Marc Serulla, Gabriel Ichim, Filip Stojceski, Gianvito Grasso, Sergii Afonin, Mathieu Heulot, Tim Schober, Robyn Roth, Cédric Godefroy, Pierre-Emmanuel Milhiet, Kushal Das, Ana J García-Sáez, Andrea Danani, Christian Widmann

Watch the movie.

TAT-RasGAP317-326 is an anti-cancer cell-penetrating peptide that was designed in our laboratory in 2004. For many years, its ability to kill tumor cells had remained a mystery. We have finally elucidated its mode of action through the use of multiple experimental approaches, including cell imaging, cell biology, in vitro vesicle biochemistry, and in silico modeling. TAT-RasGAP317-326 first penetrates cells by direct translocation through the plasma membrane and then targets inner-leaflet enriched phospholipids, such as phosphoserine and phosphatidylinositol-bisphosphate, to destabilize the cell’s membrane and induce its lysis.

Journal of Cell Science (2022)

HDLs extract lipophilic drugs from cells

Adi Zheng, Gilles Dubuis, Maria Georgieva, Carla Susana Mendes Ferreira, Marc Serulla, Maria del Carmen Conde Rubio, Evgeniya Trofimenko, Thomas Mercier, Laurent Decosterd, and Christian Widmann

This paper concludes our research on HDLs, the “good cholesterol” that was supported by a Sinergia grant from the Swiss National Science Foundation. We show in this article that HDLs utilize their capacity of loading themselves with lipophilic compounds, akin to their ability to extract cellular cholesterol, to reduce the cell content of hydrophobic drugs. This can be beneficial if lipophilic xenobiotics are toxic but may be detrimental to the therapeutic benefit of lipophilic drugs such as glibenclamide.

Christian Widmann’s articles in journals with editorial boards (R: review; C: commentary or editorial; others: original articles).

129. Marc Serulla, Palapuravan Anees, Ali Hallaj, Evgeniya Trofimenko, Tara Kalia, Yamuna Krishnan, Christian Widmann. Plasma membrane depolarization reveals endosomal escape incapacity of cell-penetrating peptides European Journal of Pharmaceutics and Biopharmaceutics 184:116-124 (2023) IF 5.6
128. Roman Mylonas, Alexandra Potts, Patrice Waridel, Jachen Barblan, Maria del Carmen Conde Rubio, Christian Widmann and Manfredo Quadroni. A database of accurate electrophoretic migration patterns for human proteins Journal of Molecular Biology 435:167933 (2023) IF 5.5
127. Maria Georgieva, Tytti Heinonen, Simone Hargraves, Trestan Pillonel, Christian Widmann*, Nicolas Jacquier*. The EnvZ/OmpR two-component system regulates the antimicrobial activity of TAT-RasGAP317-326 and the collateral sensitivity to other antibacterial agents Microbiology Spectrum 10(3):e0200921 (2022) IF 7.2
* corresponding authors and shared senior authorship
126. Daniel Constantin, Gilles Dubuis, Maria del Carmen Conde Rubio, and Christian Widmann. APOBEC3C, a nucleolar protein induced by genotoxins, is excluded from DNA damage sites FEBS Journal 289(3):803-831 (2022) IF 5.5
125. Adi Zheng, Gilles Dubuis, Maria Georgieva, Carla Susana Mendes Ferreira, Marc Serulla, Maria del Carmen Conde Rubio, Evgeniya Trofimenko, Thomas Mercier, Laurent Decosterd, and Christian Widmann. HDLs extract lipophilic drugs from cells Journal of Cell Science 135:jcs258644 (2022) IF 5.3
124. Evgeniya Trofimenko, Gianvito Grasso, Mathieu Heulot, Nadja Chevalier, Marco Deriu, Gilles Dubuis, Yoan Arribat, Marc Serulla, Sébastien Michel, Gil Vantomme, Florine Ory, Linh Chi Dam, Julien Puyal, Francesca Amati, Anitha Lüthi, Andrea Danani, and Christian Widmann. Genetic, cellular, and structural characterization of the membrane potential-dependent cell-penetrating peptide translocation pore eLife 10:e69832 (2021) IF 8.1
123. Evgeniya Trofimenko, Yuta Homma, Mitsunori Fukuda, Christian Widmann. The endocytic pathway taken by cationic substances requires Rab14 but not Rab5 and Rab7. Cell Reports 37:109945 (2021) IF 9.4
122. Maria Georgieva, Tytti Heinonen, Alessandra Vitale, Simone Hargraves, Senka Causevic, Trestan Pillonel, Leo Eberl, Christian Widmann*, Nicolas Jacquier,*. Bacterial surface properties influence the activity of the TAT-RasGAP317-326 antimicrobial peptide. iScience 24:102923 (2021) IF 5.1
* corresponding authors and shared senior authorship
121. María del Carmen Conde-Rubio, Roman Mylonas, Christian Widmann. The proteolytic landscape of cells exposed to non-lethal stresses is shaped by executioner caspases. Cell Death Discovery 7:164 (2021) IF 4.0
120. Tytti Heinonen, Simone Hargraves, Maria Georgieva, Christian Widmann, Nicolas Jacquier. The antimicrobial peptide TAT-RasGAP317-326 inhibits the formation and expansion of bacterial biofilms in vitro. Journal of Global Antimicrobial Resistance 25:227-231 (2021) IF 2.7
119. Claudiane Guay, Baroj Abdulkarim, Jennifer Y. Tan, Gilles Dubuis, Sabine Rütti, David Ross Laybutt, Christian Widmann, Romano Regazzi & Ana Claudia Marques. Loss-of-function of the long noncoding RNA A830019P07Rik in mice does not affect insulin expression and secretion. Scientific Reports 10:6413 (2020) IF 5.0
118. Marc Serulla, Gabriel Ichim, Filip Stojceski, Gianvito Grasso, Sergii Afonin, Mathieu Heulot, Tim Schober, Robyn Roth, Cédric Godefroy, Pierre-Emmanuel Milhiet, Kushal Das, Ana J García-Sáez, Andrea Danani, Christian Widmann. TAT-RasGAP317-326 kills cells by targeting inner-leaflet-enriched phospholipids. Proceedings of the National Academy of Sciences of the United States of America 117:31871-31881 (2020) IF 9.7
117. Daniel Constantin and Christian Widmann. ASH2L drives proliferation and sensitivity to bleomycin and other genotoxins in Hodgkin’s lymphoma and testicular cancer cells. Cell Death & Disease 12:1019 (2020) IF 6.5 (C)
116. Adi Zheng and Christian Widmann. The interplay between serum amyloid A and HDLs. Curr Opin Lipidol 31: 300-301 (2020) IF 3.9 (C)
115. Adi Zheng, Gilles Dubuis, Carla Susana Mendes Ferreira, Jannick Pétremand, Güliz Vanli, and Christian Widmann. CRISPR/Cas9 genome-wide screening identifies KEAP1 as a sorafenib, lenvatinib, and regorafenib sensitivity gene in hepatocellular carcinoma. Oncotarget 10:7058-7070 (2019) IF 5.2
114. Cloux AJ, Aubry D, Heulot M, Widmann C, ElMokh O, Piacente F, Cea M, Nencioni A, Bellotti A, Bouzourene K, Pellegrin M, Mazzolai L, Duchosal MA, Nahimana A.Reactive oxygen/nitrogen species contribute substantially to the antileukemia effect of APO866, a NAD lowering agent. Oncotarget 10:6723-6738 (2019) IF 5.2
113. Adi Zheng, Gilles Dubuis, Carla Susana Mendes Ferreira, Jannick Pétremand, Güliz Vanli, and Christian Widmann. The PI3K/Akt pathway is not a main driver in HDL-mediated cell protection. Cellular Signalling 62:109347 (2019) IF 3.4
112. Rosa Chiara Paolicelli and Christian Widmann. Squalene: friend or foe for cancers. Curr Opin Lipidol 30:353-354 (2019) IF 3.9 (C)
111. Giulia Torriani, Evgeniya Trofimenko, Jennifer Mayor, Chiara Fedeli, Hector Moreno, Sébastien Michel, Mathieu Heulot, Nadja Chevalier, Gert Zimmer, Neeta Shresth, Philippe Plattet, Olivier Engler, Sylvia Rothenberger, Christian Widmann*, and Stefan Kunz*. Identification of clotrimazole-derivatives asspecific inhibitors of Arenavirus fusion. Journal of Virology 93:e01744-18 (2019) IF 4.4
* corresponding authors and shared senior authorship
110. Marlen Knobloch and Christian Widmann. Burning fat to keep your stem cells? The role of fatty acid oxidation in various tissue stem cells. Curr Opin Lipidol 29:426-427 (2018) IF 3.9 (C)
109. Postovit L, Widmann C, Huang P, Gibson SB. Harnessing oxidative stress as an innovative target for cancer therapy. Oxidative Medicine and Cellular Longevity 2018:6135739 (2018) IF 4.6 (C)
108. Regazzi R and Widmann C. Fatty acid metabolism regulates cell survival in specific niches. Curr Opin Lipidol 28:284-285 (2017) IF 4.5 (C)
107. Güliz Vanli, Alvaro Cuesta-Marban, and Christian Widmann. Evaluation and validation of commercial antibodies for the detection of Shb. PLoS ONE 12:e0188311 (2017) IF 2.8
106. Mathieu Heulot, Nicolas Jacquier, Sebastien Aeby, Didier Le Roy, Thierry Roger, Evgeniya Trofimenko, David Barras, Gilbert Greub, and Christian Widmann. The anticancer peptide TAT-RasGAP317-326 exerts broad antimicrobial activity. Frontiers in Microbiology 8:994 (2017) IF 4.2
105. Pelagia Tsoutsou, Alessandro Annibaldi, David Viertl, Jonathan Ollivier, Franz Buchegger, Marie-Catherine Vozenin, Jean Bourhis, Christian Widmann*, Oscar Matzinger*. TAT-RasGAP317-326 enhances radiosensitivity of human carcinoma cell lines in vitro and in vivo through promotion of delayed mitotic cell death. Radiation Research 187:562-569 (2017) IF 3.0
* shared senior authorship
104. Güliz Vanli Jaccard, Christine Sempoux, Widmann C. The caspase-3/p120 RasGAP stress-sensing module reduces liver cancer incidence but does not affect overall survival in gamma-irradiated and carcinogen-treated mice. Molecular Carcinogenesis 56:1680-1684 (2017) IF 4.7
103. Amati F and Widmann C. Acetate is the master of its fate, genetics, and molecular biology bimonthly update. Curr Opin Lipidol 27:636-637 (2016) IF 5.3 (C)
102. Plaisance P, Brajkovic S, Tenenbaum, M, Favre D, Ezanno H, Bonnefond A, Bonner C, Gmyr V, Kerr-Conte J, Gauthier BR, Widmann C, Waeber G, Pattou F, Froguel P, Abderrahmani A. Endoplasmic reticulum stress links oxidative stress to impaired pancreatic beta-cell function caused by human oxidized LDL. PLoS ONE 11:e0163046 (2016) IF 3.1
101. Flahaut M, Jauquier N, Chevalier N, Nardou K, Balmas Bourloud K, Joseph JM, Barras D, Widmann C, Gross N, Renella R, Mühlethaler-Mottet A. Aldehyde dehydrogenase activity plays a key role in the aggressive phenotype of neuroblastoma. BMC Cancer 16:781 (2016) IF 3.3
100. Heulot M, Chevalier N, Puyal J, Margue C, Michel S, Kresi S, Kulms D, Barras D, Nahimana A, and Widmann C. The TAT-RasGAP317-326 anti-cancer peptide can kill in a caspase-, apoptosis-, and necroptosis-independent manner. Oncotarget 7:64342-64359 (2016) IF 5.0
99. Rütti S and Widmann C. Are HDL receptors really located where we think they are in the liver? Curr Opin Lipidol 27:424-425 (2016) IF 5.3 (C)
98. Rütti S and Widmann C. HDL plasticity and diversity of functions. Curr Opin Lipidol 26:596-597 (2015) IF 5.7 (C)
97. Khalil H, Loukili N, Regamey A, Cuesta-Marban A, Santori E, Huber M and Widmann C. The caspase-3/p120 RasGAP module generates a NF-kB repressor in response to cellular stress. J Cell Sci 128:3502-3513 (2015) IF 5.4
96. Cailliau K, Lescuyer A, Burnol AF, Cuesta-Marban A and Widmann C*, Browaeys-Poly E*. RasGAP shields Akt from deactivating phosphatases in fibroblast growth factor signaling but loses this ability once cleaved by caspase-3. J Biol Chem 290:19653-19665 (2015) IF 4.6
* shared senior authorship
95. Breton CS, Aubry D, Ginet V, Puyal J, Heulot M, Widmann C, Duchosal MA, and Nahimana A. Combinative effects of beta-Lapachone and APO866 on pancreatic cancer cell death through reactive oxygen species production and PARP-1 activation. Biochimie 116:141-153 (2015) IF 3.0
94. Chevalier N, Gross N and Widmann C. Assessment of the chemosensitizing activity of TAT-RasGAP317-326, a RasGAP-derived cell penetrating peptide, in childhood cancers. PLoS ONE 10:e0120487 (2015) IF 3.5
93. Neumann C, Bigliardi-Qi M, Widmann C and Bigliardi PL. The d-opioid receptor affects epidermal homeostasis via ERK-dependent inhibition of transcription factor POU2F3. J Invest Dermatol 135:471-480 (2015) IF 6.4
92. Vollenweider P, von Eckardstein A and Widmann C. HDLs, diabetes, and metabolic syndrome. Handb Exp Pharmacol 224:405-421 (2015) IF 3.6 (R)
91. Vanli G, Peltzer N, Dubuis G and Widmann C. The activity of the anti-apoptotic fragment generated by the caspase-3/p120 RasGAP stress-sensing module displays strict Akt isoform specificity. Cell. Signal 26:2992-2997 (2014) IF 4.5
90. Amati F and Widmann C. Triglyceride and HDL: the entangled pair. Curr Opin Lipidol 25:404-405 (2014) IF 5.8 (C)
89. Barras D, Chevalier N, Zoete V, Dempsey R, Lapouge K, Olayioye MA, Michielin O and Widmann C. A WXW motif is required for the anticancer activity of the TAT-RasGAP317-326 peptide. J Biol Chem 289:23701-23711 (2014) IF 4.6
88. von Eckardstein A and Widmann C. HDL, beta cells and diabetes. Cardiovasc Res 103:384-394 (2014) IF 5.8 (R)
87. Barras D and Widmann C. GAP-independent functions of DLC1 in metastasis. Cancer Metastasis Rev 33:87-100 (2014) IF 5.5 (R)
86. Barras D, Lorusso G, Lhermitte B, Ruegg C, and Widmann C. Fragment N2, a caspase-3 generated RasGAP fragment, inhibits breast cancer metastatic progression. Int J Cancer 135:242-247 (2014) IF 6.2
85. Khalil H, Bertrand MJ, Vandenabeele P, and Widmann C. Caspase-3 and RasGAP: a stress-sensing survival/demise switch. Trends Cell Biol 24:83-89 (2014) IF 11.7 (R)
84. Annibaldi A, Heulot M, Martinou JC, and Widmann C. TAT-RasGAP317-326-mediated tumor cell death sensitization can occur independently of Bax and Bak. Apoptosis 19:719-733 (2014) IF 3.9
83. Barras D, Lorusso G, Ruegg C, and Widmann C. Inhibition of cell migration and invasion mediated by the TAT-RasGAP317-326 peptide requires the DLC tumor suppressor. Oncogene 33:5163-5172 (2014) IF 8.6
82. Jaccard E and Widmann C. The control of lipid-induced inflammation by macrophages. Curr Opin Lipidol 24:528-529 (2013) IF 5.8 (C)
81. Puyal J, Petremand J, Dubuis G, Rummel C, and Widmann C. HDLs protect the MIN6 insulinoma cell line against tunicamycin-induced apoptosis without inhibiting ER stress and without restoring ER functionality. Mol Cell Endocrinol 381:291-301 (2013) IF 4.0
80. Peltzer N, Vanli G, Yang JY, and Widmann C. Role of mTOR, Bad, and Survivin in RasGAP fragment N-mediated cell protection. PLoS ONE 8:e68123-(2013) IF 4.1
79. Widmann C. HDL-endoplasmic reticulum connection and cholesterol sensor. Curr Opin Lipidol 24:103-104 (2013) IF 6.1 (C)
78. Khalil H, Peltzer N, Walicki J, Yang JY, Dubuis G, Gardiol N, Held W, Bigliardi P, Marsland B, Liaudet L, and Widmann C. Caspase-3 protects stressed organs against cell death. Mol Cell Biol 32:4523-4533 (2012) IF 5.5
77. Khalil H, Rosenblatt N, Liaudet L, and Widmann C. The role of endogenous and exogenous RasGAP-derived fragment N in protecting cardiomyocytes from peroxynitrite-induced apoptosis. Free Radic Biol Med 53:926-935 (2012) IF 5.4
76. Peltzer N, Bigliardi P, and Widmann C. UV-B induces cytoplasmic survivin expression in mouse epidermis. J Dermatol Sci 67:196-199 (2012) IF 3.7
75. Petremand J, Puyal J, Chatton JY, Duprez J, Allagnat F, Frias M, James RW, Waeber G, Jonas JC, and Widmann C. HDLs protect pancreatic beta-cells against ER stress by restoring protein folding and trafficking. Diabetes 61:1100-1111 (2012) IF 8.9
74. Regazzi R and Widmann C. miRNAs take the HDL ride. Curr Opin Lipidol 23:165-166 (2012) IF 6.6 (C)
73. Annibaldi A, Dousse A, Martin S, Tazi J, and Widmann C. Revisiting G3BP1 as a RasGAP binding protein: sensitization of tumor cells to chemotherapy by the RasGAP 3127-326 sequence does not involve G3BP1. PLoS ONE 6:e29024 (2011) IF 4.4
72. Bulat N, Jaccard E, Peltzer N, Khalil H, Yang JY, Dubuis G, and Widmann C. RasGAP-derived fragment N increases the resistance of beta cells towards apoptosis in NOD mice and delays the progression from mild to overt diabetes. PLoS ONE 6:e22609 (2011) IF 4.4
71. Petremand J and Widmann C. Fatty acids and endoplasmic reticulum stress. Curr Opin Lipidol 22:315-316 (2011) IF 6.6 (C)
70. Barras D and Widmann C. Promises of apoptosis-inducing peptides in cancer therapeutics. Curr Pharm Biotechnol 12:1153-1165 (2011) IF 3.4 (R)
69. Islam MR, Jimenez T, Pelham C, Rodova M, Puri S, Magenheimer BS, Maser RL, Widmann C, and Calvet JP. MAP/ERK kinase kinase 1 (MEKK1) mediates transcriptional repression by interacting with polycystic kidney disease-1 (PKD1) promoter-bound p53 tumor suppressor protein. J Biol Chem 285: 38818-38831 (2010) IF 5.3
68. Petremand J and Widmann C. The HDL: adipocyte connection. Curr Opin Lipidol 21: 388-389 (2010) IF 6.1 (C)
67. Annibaldi A and Widmann C. Glucose metabolism in cancer cells. Curr Opin Clin Nutr Metab Care 13: 466-470 (2010). IF 4.3 (R)
66. Jaccard E and Widmann C. ABC transporters: HDL-regulated gatekeepers at the endothelial border. Curr Opin Lipidol 20: 526-527 (2009). IF 3.7 (C)
65. Yang JY, Walicki J, Jaccard E, Dubuis G, Bulat N, Hornung JP, Thorens B, and Widmann C. Expression of the NH2-terminal fragment of RasGAP in pancreatic b-cells increases their resistance to stresses and protects mice from diabetes. Diabetes 58: 2596-2606 (2009). IF 8.4
64. Petremand J, Bulat N, Butty AC, Poussin C, Rutti S, Au K, Ghosh S, Mooser V, Thorens B, Yang JY, Widmann C*#, and Waeber G*. Involvement of 4E-BP1 in the protection induced by HDLs on pancreatic beta cells. Mol Endocrinol 23: 1572-1586 (2009). IF 5.4 (#, corresponding author; *shared senior authorship)
63. Bulat N and Widmann C. Caspase substrates and neurodegenerative diseases. Brain Res Bull 80: 251-267 (2009). IF 2.3 (R)
62. Cornu M, Yang JY, Jaccard E, Poussin C, Widmann C, and Thorens B. Glucagon-like peptide-1 protects beta-cells against apoptosis by increasing the activity of an IGF-2/IGF-1 receptor autocrine loop. Diabetes 58: 1816-1825 (2009). IF 8.4
61. Michod D, Annibaldi A, Schaefer S, Dapples C, Rochat B, and Widmann C. Effect of RasGAP N2 fragment-derived peptide on tumor growth in mice. J Natl Cancer Inst 101: 828-832 (2009). IF 15.7
60. Jaccard E and Widmann C. So, so complex HDLs! Curr Opin Lipidol 20: 254-255 (2009). IF 3.7 (C)
59. Annibaldi A, Michod D, Vanetta L, Cruchet S, Nicod P, Dubuis G, Bonvin C, and Widmann C. Role of the sub-cellular localization of RasGAP fragment N2 for its ability to sensitize cancer cells to genotoxin-induced apoptosis. Exp Cell Res 315: 2081-2091 (2009). IF 3.7
58. Bulat N, Waeber G, and Widmann C. LDLs stimulate p38 MAPKs and wound healing through SR-BI independently of Ras and PI3 kinase. J Lipid Res 50: 81-89 (2009). IF 4.3
57. Plaisance V, Perret V, Favre D, Abderrahmani A, Yang JY, Widmann C, and Regazzi R. Role of the transcriptional factor C/EBPb in free fatty acid-elicited b-cell failure. Mol Cell Endocrinol 305: 47-55 (2009). IF 3.0
56. Petremand J and Widmann C. Sphingolipids – from membrane constituents to signaling molecules that control cell-to-cell communications. Curr Opin Lipidol 19: 620-621 (2008). IF 6.2 (C)
55. Lovis P, Roggli E, Laybutt DR, Gattesco S, Yang JY, Widmann C, Abderrahmani A, and Regazzi R. Alterations in microRNA expression contribute to fatty acid-induced pancreatic beta-cell dysfunction. Diabetes 57: 2728-2736 (2008). IF 8.0
54. Bulat N and Widmann C. Generation of a tightly regulated all-cis b cell-specific tetracycline-inducible vector. BioTechniques 45: 411-420 (2008). IF 2.5
53. Ferdaoussi M, Abdelli S, Yang JY, Cornu M, Niederhauser G, Favre D, Widmann C, Regazzi R, Thorens B, Waeber G, and Abderrahmani A. Exendin-4 protects b-cells from interleukin-1b-induced apoptosis by interfering with the c-Jun NH2-terminal kinase pathway. Diabetes 57: 1205-1215 (2008). IF 8.0
52. Petremand J, Abderrahmani A, and Widmann C. Genetics and molecular biology: HDLs and their multiple ways to protect cells. Curr Opin Lipidol 19: 95-97 (2008). IF 6.2 (C)
51. Yang J-Y, Moulin N, van Bemmelen MX, Dubuis G, Tawadros T, Haefliger J-A, Waeber G, and Widmann C. Splice variant-specific stabilization of JNKs by IB1/JIP1. Cell Signal 19: 2201-2207 (2007). IF 4.9
50. Abderrahmani A, Niederhauser G, Favre D, Abdelli S, Ferdaoussi M, Yang JY, Regazzi R, Widmann C, and Waeber G. Human high-density lipoprotein particles prevent activation of the JNK pathway induced by human oxidised low-density lipoprotein particles in pancreatic b cells. Diabetologia 50: 1304-1314 (2007). IF 5.3
49. Pittet O, Petermann D, Michod D, Krueger T, Cheng C, Ris HB, and Widmann C. Effect of the TAT-RasGAP317-326 peptide on apoptosis of human malignant mesothelioma cells and fibroblasts exposed to meso-tetra-hydroxyphenyl-chlorin and light. J Photochem Photobiol B 88: 29-35 (2007). IF 1.6
48. Michod D and Widmann C. DNA-damage sensitizers: potential new therapeutical tools to improve chemotherapy. Crit Rev Oncol Hematol 63: 160-171 (2007). IF 3.0 (R)
47. Michod D and Widmann C. TAT-RasGAP317-326 requires p53 and PUMA to sensitize tumor cells to genotoxins. Mol Cancer Res 5: 497-507 (2007). IF 5.4
46. Ross B, Kristensen O, Favre D, Walicki J, Kastrup JS, Widmann C, and Gajhede M. High resolution crystal structures of the p120 RasGAP SH3 domain. Biochem Biophys Res Commun 353: 463-468 (2007). IF 3.0
45. Dobreva I, Waeber G, and Widmann C. Lipoproteins and mitogen-activated protein kinase signaling: a role in atherogenesis? Curr Opin Lipidol 17: 110-121 (2006). IF 5.3 (R)
44. Dobreva I, Waeber G, James RW, and Widmann C. IL-8 secretion by fibroblasts induced by low-density lipoproteins is p38 MAPK-dependent and leads to cell spreading and wound closure. J Biol Chem 281: 199-205 (2006). IF 5.9
43. Yang J-Y, Walicki J, Abderrahmani A, Cornu M, Waeber G, Thorens B, and Widmann C. Expression of an uncleavable N-terminal RasGAP fragment in insulin-secreting cells increases their resistance toward apoptotic stimuli without affecting their glucose-induced insulin secretion. J Biol Chem 280: 32835-32842 (2005). IF 6.4
42. Dobreva I, Zschörnig O, James RW, Waeber G, and Widmann C. Cholesterol is the major component of native lipoproteins activating the p38 MAPKs. Biol Chem 368: 909-918 (2005). IF 3.4
41. Yang J-Y, Walicki J, Michod D, Dubuis G, and Widmann C. Impaired Akt activity down-modulation, caspase-3 activation, and apoptosis in cells expressing a caspase-resistant mutant of RasGAP at position 157. Mol Biol Cell 16: 3511-3520 (2005). IF 7.5
40. Michod D, Yang JY, Chen J, Bonny C, and Widmann C. A RasGAP-derived cell permeable peptide potently enhances genotoxin-induced cytotoxicity in tumor cells. Oncogene 23: 8971-8978 (2004). IF 6.5
39. Yang J-Y, Michod D, Walicki J, Murphy BM, Kasibhatla S, Martin S, and Widmann C. Partial cleavage of RasGAP by caspases is required for cell survival in mild stress conditions. Mol Cell Biol 24: 10425-10436 (2004). IF 8.1
38. Yang J-Y, Michod D, Walicki J, and Widmann C. Surviving the kiss of death. Biochem Pharmacol 68: 1027-1031 (2004). IF 3.0 (R)
37. Moulin N and Widmann C. Islet-brain (IB)/JNK-interacting proteins (JIPs): future targets for the treatment of neurodegenerative diseases? Curr Neurovasc Res 1: 111-127 (2004). IF 3.6 (R)
36. Bartling B, Yang JY, Michod D, Widmann C, Lewensohn R, and Zhivotovsky B. RasGTPase-activating protein is a target of caspases in spontaneous apoptosis of lung carcinoma cells and in response to etoposide. Carcinogenesis 25: 909-921 (2004). IF 4.7
35. Dobreva I, Waeber G, Mooser V, James RW, and Widmann C. LDLs induce fibroblast spreading independently of the LDL receptor via activation of the p38 MAPK pathway. J Lipid Res 44: 2382-2390 (2003). IF 3.9
34. Yang J-Y and Widmann C. A subset of caspase substrates functions as the Jekyll and Hyde of apoptosis. Eur Cytokine Netw 13: 387 (2002). IF 2.4
33. Yang J-Y and Widmann C. The RasGAP N-terminal fragment generated by caspase cleavage protects cells in a Ras/PI3K/Akt-dependent manner that does not rely on NFkB activation. J Biol Chem 277: 14641-14646 (2002). IF 7.4
32. Schlesinger TK, Bonvin C, Jarpe MB, Fanger GR, Cardinaux J-R, Johnson GL, and Widmann C. Apoptosis stimulated by the 91-kDa caspase cleavage MEKK1 fragment requires translocation to soluble cellular compartments. J Biol Chem 277: 10283-10291 (2002). IF 7.4
31. Bonvin C, Guillon A, van Bemmelen MX, Gerwins P, Johnson GL, and Widmann C. Role of the amino-terminal domains of MEKKs in the activation of NFkB and MAPK pathways and in the regulation of cell proliferation and apoptosis. Cell Signal 14: 123-131 (2002). IF 3.5
30. Clarke P, Meintzer SM, Widmann C, Johnson GL, and Tyler KL. Reovirus Infection Activates JNK and the JNK-Dependent Transcription Factor c-Jun. J Virol 75: 11275-11283 (2001). IF 5.8
29. Yang J-Y and Widmann C. Antiapoptotic signaling generated by caspase-induced cleavage of RasGAP. Mol Cell Biol 21: 5346-5358 (2001). IF 9.9
28. Widmann C, Sather S, Oyer R, Johnson GL, and Dreskin SC. In vitro activity of MEKK2 and MEKK3 in detergents is a function of a valine to serine difference in the catalytic domain. Biochim Biophys Acta 1547: 167-173 (2001). IF 2.6
27. Clarke P, Meintzer SM, Gibson S, Widmann C, Garrington TP, Johnson GL, and Tyler KL. Reovirus-induced apoptosis is mediated by TRAIL. J Virol 74: 8135-8139 (2000). IF 5.8
26. Yujiri T, Ware M, Widmann C, Oyer R, Russell D, Chan E, Zaitsu Y, Clarke P, Tyler K, Oka Y, Fanger GR, Henson P, and Johnson GL. MEK kinase 1 gene disruption alters cell migration and c-Jun NH2- terminal kinase regulation but does not cause a measurable defect in NFkB activation. Proc Natl Acad Sci USA 97: 7272-7277 (2000). IF 9.8
25. Pellet JB, Haefliger JA, Staple JK, Widmann C, Welker E, Hirling H, Bonny C, Nicod P, Catsicas S, Waeber G, and Riederer BM. Spatial, temporal and subcellular localization of islet-brain 1 (IB1), a homologue of JIP-1, in mouse brain. Eur J Neurosci 12: 621-632 (2000). IF 3.8
24. Waeber G, Delplanque J, Bonny C, Mooser V, Steinmann M, Widmann C, Maillard A, Miklossy J, Dina C, Hani H, Vionnet N, Nicod P, Boutin P, and Froguel P. The gene MAPK8IP1, encoding islet-brain-1, is a candidate for type 2 diabetes. Nat Genet 24: 291-295 (2000). IF 40.4
23. Widmann C, Gibson S, Jarpe MB, and Johnson GL. MAPK pathways: conservation of a three-kinase module from yeast to man. Physiol Rev 79: 143-180 (1999). IF 23.7 (R)
22. Gibson S, Widmann C, and Johnson GL. Differential involvement of MEK kinase 1 (MEKK1) in the induction of apoptosis in response to microtubule-targeted drugs versus DNA damaging agents. J Biol Chem 274: 10916-10922 (1999). IF 7.2
21. Jarpe MB, Widmann C, Knall C, Schlesinger TK, Gibson S, Yujiri T, Fanger GR, Gelfand EG, and Johnson GL. Anti-apoptotic versus pro-apoptotic signal transduction: checkpoints and stop signs along the road to death. Oncogene 17: 1475-1482 (1998). IF 6.2 (R)
20. Widmann C, Gibson S, and Johnson GL. Caspase-dependent cleavage of signaling proteins during apoptosis. A turn-off mechanism for anti-apoptotic signals. J Biol Chem 273: 7141-7147 (1998). IF 7.2
19. Widmann C, Gerwins P, Lassignal Johnson N, Jarpe MB, and Johnson GL. MEKK1, a substrate for DEVD-directed caspases, is involved in genotoxin-induced apoptosis. Mol Cell Biol 18: 2416-2429 (1998). IF 9.6
18. Fanger GR, Widmann C, Porter AC, Sather S, Johnson GL, and Vaillancourt RR. 14-3-3 proteins interact with specific MEK kinases. J Biol Chem 273: 3476-3483 (1998). IF 7.2
17. Widmann C, Lassignal Johnson N, Gardner AM, Smith RJ, and Johnson GL. Potentiation of apoptosis by low dose stress stimuli in cells expressing activated MEK kinase 1. Oncogene 15: 2439-2447 (1997). IF 6.2
16. Cardone M, Salvesen GS, Widmann C, Johnson GL, and Frisch SM. The regulation of anoikis: MEKK-1 activation requires cleavage by caspases. Cell 90: 315-323 (1997). IF 38.7
15. Widmann C, Dolci W, and Thorens B. Internalization and homologous desensitization of the GLP-1 receptor depend on phosphorylation of the receptor carboxyl tail at the same three sites. Mol Endocrinol 11: 1094-1102 (1997). IF 7.9
14. Fanger GR, Gerwins P, Widmann C, Jarpe MB, and Johnson GL. MEKKs, GCKs, MLKs, PAKs, TAKs, and Tpls: upstream regulators of the c-Jun amino-terminal kinases? Curr Opin Genet Dev 7: 67-74 (1997). IF 11.0 (R)
13. Eberl G, Widmann C, and Corradin G. The functional half-life of H-2Kd-restricted T cell epitopes on living cells. Eur J Immunol 26: 1993-1999 (1996). IF 5.4
12. Widmann C, Dolci W, and Thorens B. Heterologous Desensitization of the Glucagon-like Peptide-1 Receptor by Phorbol Esters Requires Phosphorylation of the Cytoplasmic Tail at Four Different Sites. J Biol Chem 271: 19957-19963 (1996). IF 7.2
11. Thorens B and Widmann C. Signal transduction and desensitization of the glucagon-like peptide-1 receptor. Acta Physiol Scand 157: 317-319 (1996). IF 1.3 (R)
10. Widmann C, Dolci W, and Thorens B. Desensitization and phosphorylation of the glucagon-like peptide-1 (GLP-1) receptor by GLP-1 and 4-phorbol 12-myristate 13-acetate. Mol Endocrinol 10: 62-75 (1996). IF 7.9
9. Widmann C, Dolci W, and Thorens B. Agonist-induced internalization and recycling of the glucagon-like peptide-1 receptor in transfected fibroblasts and in insulinomas. Biochem J 310: 203-214 (1995). IF 3.9
8. Widmann C, Bürki E, Dolci W, and Thorens B. Signal transduction by the cloned glucagon-like peptide-1 receptor: comparison with signalling by the endogenous receptors of b cell lines. Mol Pharmacol 45: 1029-1035 (1994). IF 5.4
7. Thorens B, Porret A, Bühler L, Deng S-P, Morel P, and Widmann C. Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin- (9-39) an antagonist of the receptor. Diabetes 42: 1678-1682 (1993). IF 8.5
6. Widmann C, Romero P, Maryanski JL, Corradin G, and Valmori D. T helper epitopes enhance the cytotoxic response of mice immunized with MHC class I-restricted malaria peptides. J Immunol Methods 155: 95-99 (1992). IF 1.9
5. Casanova J-L, Cerottini J-C, Matthes M, Necker A, Gournier H, Barra C, Widmann C, MacDonald HR, Lemonnier FA, Malissen B, and Maryanski JL. H-2-restricted cytolytic T lymphocytes specific for HLA display T cell receptors of limited diversity. J Exp Med 176: 439-447 (1992). IF 15.9
4. Romero P, Eberl G, Casanova J-L, Cordey A-S, Widmann C, Luescher IF, Corradin G, and Maryanski JL. Immunization with synthetic peptides containing a defined malaria epitope induces a highly diverse CTL response. Evidence that two peptides residue are burried in the MHC molecule. J Immunol 148: 1871-1878 (1992). IF 7.2
3. Casanova J-L, Romero P, Widmann C, Kourilsky P, and Maryanski JL. T-cell receptor genes in a series of class I MHC restricted CTL clones specific for a Plasmodium berghei nonapeptide. J Exp Med 174: 1371-1383 (1991). IF 15.9
2. Widmann C, Maryanski JL, Romero P, and Corradin G. Differential stability of antigenic MHC class I-restricted synthetic peptides. J Immunol 147: 3745-3751 (1991). IF 7.2
1. Demotz S, Lanzavecchia A, Eisel U, Niemann H, Widmann C, and Corradin G. Delineation of several DR-restricted tetanus toxin T cell epitopes. J Immunol 142: 394-402 (1989). IF 7.2