A mechanism for inhibiting the SUMO pathway - PubMed (original) (raw)
A mechanism for inhibiting the SUMO pathway
Roberto Boggio et al. Mol Cell. 2004.
Free article
Abstract
The SUMO pathway parallels the classical ubiquitinylation pathway with three discrete steps: activation involving the enzyme E1, conjugation involving the E2 enzyme UBC9, and substrate modification through the cooperative association of UBC9 and E3 ligases. We report here that the adenoviral protein Gam1 inhibits the SUMO pathway by interfering with the activity of E1 (SAE1/SAE2). In vivo, Gam1 expression leads to SAE1/SAE2 inactivation, both SAE1/SAE2 and UBC9 disappearance, and overall inhibition of protein sumoylation. This results in transcriptional activation of some promoters and is directly linked to inhibition of sumoylation of the transcriptional activators involved. Our results identify a mechanism for interfering with the SUMO pathway and with transcription that could have an impact in the design of novel pharmaceutical agents. They also point out once again to the extraordinary ability of eukaryotic viruses to interfere with the biology of host cells by targeting fundamental biochemical processes.
Similar articles
- Viral control of the SUMO pathway: Gam1, a model system.
Chiocca S. Chiocca S. Biochem Soc Trans. 2007 Dec;35(Pt 6):1419-21. doi: 10.1042/BST0351419. Biochem Soc Trans. 2007. PMID: 18031235 Review. - Role of an N-terminal site of Ubc9 in SUMO-1, -2, and -3 binding and conjugation.
Tatham MH, Kim S, Yu B, Jaffray E, Song J, Zheng J, Rodriguez MS, Hay RT, Chen Y. Tatham MH, et al. Biochemistry. 2003 Aug 26;42(33):9959-69. doi: 10.1021/bi0345283. Biochemistry. 2003. PMID: 12924945 - Targeting SUMO E1 to ubiquitin ligases: a viral strategy to counteract sumoylation.
Boggio R, Passafaro A, Chiocca S. Boggio R, et al. J Biol Chem. 2007 May 25;282(21):15376-82. doi: 10.1074/jbc.M700889200. Epub 2007 Mar 28. J Biol Chem. 2007. PMID: 17392274 - Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9.
Tatham MH, Jaffray E, Vaughan OA, Desterro JM, Botting CH, Naismith JH, Hay RT. Tatham MH, et al. J Biol Chem. 2001 Sep 21;276(38):35368-74. doi: 10.1074/jbc.M104214200. Epub 2001 Jul 12. J Biol Chem. 2001. PMID: 11451954 - Gam1 and the SUMO pathway.
Boggio R, Chiocca S. Boggio R, et al. Cell Cycle. 2005 Apr;4(4):533-5. doi: 10.4161/cc.4.4.1605. Epub 2005 Apr 15. Cell Cycle. 2005. PMID: 15876861 Review.
Cited by
- Trojan horse strategies used by pathogens to influence the small ubiquitin-like modifier (SUMO) system of host eukaryotic cells.
Békés M, Drag M. Békés M, et al. J Innate Immun. 2012;4(2):159-67. doi: 10.1159/000335027. Epub 2012 Jan 3. J Innate Immun. 2012. PMID: 22223032 Free PMC article. Review. - Adenovirus E1B 55-kilodalton protein is a p53-SUMO1 E3 ligase that represses p53 and stimulates its nuclear export through interactions with promyelocytic leukemia nuclear bodies.
Pennella MA, Liu Y, Woo JL, Kim CA, Berk AJ. Pennella MA, et al. J Virol. 2010 Dec;84(23):12210-25. doi: 10.1128/JVI.01442-10. Epub 2010 Sep 22. J Virol. 2010. PMID: 20861261 Free PMC article. - Listeria monocytogenes impairs SUMOylation for efficient infection.
Ribet D, Hamon M, Gouin E, Nahori MA, Impens F, Neyret-Kahn H, Gevaert K, Vandekerckhove J, Dejean A, Cossart P. Ribet D, et al. Nature. 2010 Apr 22;464(7292):1192-5. doi: 10.1038/nature08963. Nature. 2010. PMID: 20414307 Free PMC article. - Allosteric Inhibition of Ubiquitin-like Modifications by a Class of Inhibitor of SUMO-Activating Enzyme.
Li YJ, Du L, Wang J, Vega R, Lee TD, Miao Y, Aldana-Masangkay G, Samuels ER, Li B, Ouyang SX, Colayco SA, Bobkova EV, Divlianska DB, Sergienko E, Chung TDY, Fakih M, Chen Y. Li YJ, et al. Cell Chem Biol. 2019 Feb 21;26(2):278-288.e6. doi: 10.1016/j.chembiol.2018.10.026. Epub 2018 Dec 20. Cell Chem Biol. 2019. PMID: 30581133 Free PMC article. - The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition.
Gareau JR, Lima CD. Gareau JR, et al. Nat Rev Mol Cell Biol. 2010 Dec;11(12):861-71. doi: 10.1038/nrm3011. Nat Rev Mol Cell Biol. 2010. PMID: 21102611 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous