Parent Category: Laboratoires Published: Thursday, 16 February 2012

Ubiquitin-like molecules and response to cellular stress

 altDimitris P. XIRODIMAS

 

 CRBM - UMR 5237

 1919, route de Mende, 34293 Montpellier

 

Phone: +33 4 34 35 95 33

Email: dimitris.xirodimas@crbm.cnrs.fr

 

 

Website

 

 

 

Post-translational modifications with ubiquitin and ubiquitin-like (Ubl) molecules such as SUMO and NEDD8 are key regulators of protein stability and function. These pathways are also major targets for Pharmaceutical companies for therapeutic intervention. Our research is focussed on the Ubl NEDD8, which has the highest homology and identity to ubiquitin, but a distinct conjugation pathway exists that leads to its covalent conjugation to substrate proteins. Genetic experiments have demonstrated a vital role for NEDD8 in cell growth, viability and development. However, compared to ubiquitination or SUMO conjugation, much less is known about molecular targets and pathways controlled by NEDD8. Our goal is to identify and characterize novel targets and functions for NEDD8 and mechanisms of regulation of NEDDylation. This becomes increasingly important as inhibitors of NEDDylation are in clinical trials for the treatment of cancer. Our group develops a multi-disciplinary research programme. We are combining biochemical and biological methods with innovative quantitative (SILAC) proteomic and microscopy approaches in mammalian and animal model systems (C. elegans). Our current research is focussed on:

1. The role of NEDD8 in the coordination between cell cycle and cell growth-Regulation of signalling from the nucleolus

2. The role of NEDD8 in the DNA damage-induced apoptosis

 

Keywords: Ubiquitin-like molecules, NEDD8, cell cycle-growth, nucleolus, DNA damage

 

 

Main publications

  • Mahata B, Sundqvist A and Xirodimas DP. Recruitment of L11RP at promoter sites of p53-regulated genes upon nucleolar stress through NEDD8 and Mdm2 dependent manner. (2011). Oncogene [Epub ahead of print]
  • Larance M*, Bailly A*, Hay R, Xirodimas DP, Gartner A and Lamond A. (2011). Stable Isotope Labeling with Amino acids in Nematodes Nature Methods 8(10):849-51 * Equal author contribution
  • Alexandru G, Pariente N and Xirodimas DP. In the family with ubiquitin. (2011). EMBO reports 12(9):880-2
  • Liu, G and Xirodimas DP (2010). NUB-1 controls the localization of p53 through co-operation of the NEDD8 and ubiquitin pathways. Oncogene 29(15):2252-61
  • Tatham MH, Rodriguez MS, Xirodimas DP and Hay RT (2009). Detection of protein SUMOylation in vivo. Nature protocols; 4(9):1362-71.
  • Sundqvist A, Liu G, Mirsaliotis A and Xirodimas DP (2009). Regulation of nucleolar signaling to p53 through NEDDylation of L11. EMBO reports;10(10):1132-9.
  • Xirodimas DP*, Sundqvist A, Nakamura A, Shen L, Botting C and Ronald T. Hay (2008). Ribosomal proteins are targets for the NEDD8 pathway. EMBO reports ; 9(3):280-6. * corresponding author
  • Shen LN, Liu H, Dong C, Xirodimas D, Naismith JH, Hay RT (2005). Structural basis of NEDD8 ubiquitin discrimination by the deNEDDylating enzyme NEDP1. EMBO J.;24(7):1341-51.
  • Xirodimas DP, Saville MK, Bourdon JC, Hay RT, Lane DP (2004). MDM2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity. Cell. ; 118(1):83-97.
  • Xirodimas DP, Saville MK, Edling C, Lane DP and Lain S. (2001). Different effects of p14ARF on the levels of ubiquitinated p53 and MDM2 in vivo. Oncogene 20(36):4972-83.

LOGO original RVB petit Logo MUSE EN Original ANR LOGO Investirlavenir CMJN1 copie Inserm Logo80ANS COMBINE OR eng logo IRD 2016 BLOC FR COUL a partir de 2017