Preferences help
enabled [disable] Abstract
Number of results
2008 | 55 | 4 | 681-686
Article title

Developmental regulation of Ubc9 in the rat nervous system

Title variants
Languages of publication
The SUMO-conjugating enzyme Ubc9 is an essential enzyme in the SUMO (small ubiquitin-related modifier) protein modification system. Although sumoylation, covalent modification of cellular proteins by SUMO, is considered to regulate various cellular processes, and many substrates for sumoylation have been identified recently, the regulation of Ubc9 expression has not been examined in detail. We analyzed the expression of Ubc9 during rat brain development at the mRNA and protein levels. Northern and Western blot analyses revealed that expression of Ubc9 and SUMO-1 was developmentally regulated, while that of the ubiquitin-conjugating enzyme UbcH7 did not change so dramatically. In situ hybridization analysis revealed that the expression of Ubc9 was high in neuronal stem cells and moderate in differentiated neurons at embryonic stages. In the adult brain, moderate expression was observed in subsets of neurons, such as the dentate granular neurons and pyramidal neurons in the hippocampal formation and the large pyramidal neurons in the cerebral cortex. These results suggest that the Ubc9-SUMO system might participate in the proliferation and differentiation of neuronal cells in the developing brain and in neuronal plasticity in the adult brain.
Physical description
  • Mitsubishi Kagaku Institute of Life Sciences, Tokyo, Japan
  • Mitsubishi Kagaku Institute of Life Sciences, Tokyo, Japan
  • Mitsubishi Kagaku Institute of Life Sciences, Tokyo, Japan
  • Department of Neurology and Neurological Science, Graduate School of Medic≠ Tokyo Medical and Dental University, Tokyo, Japan
  • Mitsubishi Kagaku Institute of Life Sciences, Tokyo, Japan
  • Desterro JM, Rodriguez MS, Hay RT (1998) SUMO-1 modification of IκBα inhibits NF-κB activation. Mol Cell 2: 233-239.
  • Dohmen RJ (2004) SUMO protein modification. Biochim Biophys Acta 1695: 113-131.
  • Eizenberg O, Faber-Elman A, Gottlieb E, Oren M, Rotter V, Schwartz M (1996) p53 plays a regulatory role in differentiation and apoptosis of central nervous system-associated cells. Mol Cell Biol 16: 5178-5185.
  • Golebiowski F, Szulc A, Sakowicz M, Szutowicz A, Pawelczyk T (2003) Expression level of Ubc9 protein in rat tissues. Acta Biochim Polon 50: 1065-1073.
  • Gocke CB, Yu H, Kang J (2005) Systematic identification and analysis of mammalian small ubiquitin-like modifier substrates. J Biol Chem 280: 5004-5012.
  • Gostissa M, Hengstermann A, Fogal V, Sandy P, Schwarz SE, Scheffner M, Del Sal G (1999) Activation of p53 by conjugation to the ubiquitin-like protein SUMO-1. EMBO J 18: 6462-6471.
  • Hateboer G, Hijmans EM, Nooij JB, Schlenker S, Jentsch S, Bernards R (1996) mUBC9, a novel adenovirus E1A-interacting protein that complements a yeast cell cycle defect. J Biol Chem 271: 25906-25911.
  • Hay RT (2005) SUMO: a history of modification. Mol Cell 18: 1-12.
  • Hochstrasser M (1996) Ubiquitin-dependent protein degradation. Ann Rev Genet 30: 405-439.
  • Johnson ES (2004) Protein modification by SUMO. Annu Rev Biochem 73: 355-382.
  • Li T, Evdokimov E, Shen RF, Chao CC, Tekle E, Wang T, Stadtman ER, Yang DC, Chock PB (2004) Sumoylation of heterogeneous nuclear ribonucleoproteins, zinc finger proteins, and nuclear pore complex proteins: a proteomic analysis. Proc Natl Acad Sci USA 101: 8551-8556.
  • Loveys DA, Streiff MB, Schaefer TS, Kato GJ (1997) The mUBC9 murine ubiquitin conjugating enzyme interacts with E2A transcriptional factors. Gene 201: 169-177.
  • Martin S, Wilkinson KA, Nishimune A, Henley JM (2007) Emerging extranuclear roles of protein SUMOylation in neuronal function and dysfunction. Nat Rev Neurosci 8: 948-959.
  • Mattson MP, Camandola S (2001) NF-κB in neuronal plasticity and neurodegenerative disorders. J Clin Invest 107: 247-254.
  • Mao Y, Desai SD, Liu LF (2000a) SUMO-1 conjugation to human DNA topoisomerase II isozymes. J Biol Chem 275: 26066-26073.
  • Mao Y, Sun M, Desai SD, Liu LF (2000b) SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damage. Proc Natl Acad Sci USA 97: 4046-4051.
  • Rodriguez MS, Desterro JM, Lain S, Midgley CA, Lane DP, Hay RT (1999) SUMO-1 modification activates the transcriptional response of p53. EMBO J 18: 6455-6461.
  • Riquelme C, Barthel KK, Liu X (2006a) SUMO-1 modification of MEF2A regulates its transcriptional activity. J Cell Mol Med 10: 132-144.
  • Riquelme C, Barthel KK, Qin XF, Liu X (2006b) Ubc9 expression is essential for myotube formation in C2C12. Exp Cell Res 312: 2132-2141.
  • Scheschonka A, Tang Z, Betz H (2007) Sumoylation in neurons: nuclear and synaptic roles? Trends Neurosci 30: 85-91.
  • Shalizi A, Gaudilliere B, Yuan Z, Stegmuller J, Shirogane T, Ge Q, Tan Y, Schulman B, Harper JW, Bonni A (2006) A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation. Science 311: 1012-1017.
  • Takahashi K, Liu FC, Hirokawa K, Takahashi H (2003) Expression of Foxp2, a gene involved in speech and language, in the developing and adult striatum. J Neurosci Res 73: 61-72.
  • Vertegaal AC, Andersen JS, Ogg SC, Hay RT, Mann M, Lamond AI (2006) Distinct and overlapping sets of SUMO-1 and SUMO-2 target proteins revealed by quantitative proteomics. Mol Cell Proteomics 5: 2298-22310.
  • Watanabe TK, Fujiwara T, Kawai A, Shimizu F, Takami S, Hirano H, Okuno S, Ozaki K, Takeda S, Shimada Y, Nagata M, Takaichi A, Takahashi E, Nakamura Y, Shin S (1996) Cloning, expression, and mapping of UBE2I, a novel gene encoding a human homologue of yeast ubiquitin-conjugating enzymes which are critical for regulating the cell cycle. Cytogenet Cell Genet 72: 86-89.
  • Wang ZY, Qiu QQ, Seufert W, Taguchi T, Testa JR, Whitmore SA, Callen DF, Welsh D, Shenk T, Deuel TF (1996) Molecular cloning of the cDNA and chromosome localization of the gene for human ubiquitin-conjugating enzyme 9. J Biol Chem 271: 24811-24816.
  • Yasugi T, Howley PM (1996) Identification of the structural and functional human homolog of the yeast ubiquitin conjugating enzyme UBC9. Nucleic Acids Res 24: 2005-2010.
  • Yates LL, Gorecki DC (2006) The nuclear factor-kappaB (NF-κB): from a versatile transcription factor to a ubiquitous therapeutic target. Acta Biochim Polon 53: 651-662.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.