SUMO: a regulator of gene expression and genome integrity

Müller, Stefan; Ledl, Andreas; Schmidt, D

doi:10.1038/sj.onc.1207415

Cited by 257 publications

(272 citation statements)

References 124 publications

Supporting

Mentioning

262

Contrasting

Unclassified

Order By: Relevance

“…Sumoylation of transcription factors and co-factors inhibits transcription in most cases and activates transcription in others (Seeler and Dejean, 2003;Johnson, 2004;Muller et al, 2004). We found that sumoylation of Ets-1 leads to reduced transcription, with the sumoylation defective mutants having a greater capacity to activate transcription than Ets-1.…”

Section: Discussionmentioning

confidence: 74%

Regulation of the Ets-1 transcription factor by sumoylation and ubiquitinylation

Degerny

Vintonenko

et al. 2006

Oncogene

View full text Add to dashboard Cite

Sumoylation and ubiquitinylation reversibly regulate the activity of transcription factors through covalent attachment to lysine residues of target proteins. We examined whether the Ets-1 transcription factor is modified by sumoylation and/or ubiquitinylation. Among four potential SUMO motifs in Ets-1, we identified lysines 15 and 227 within the LK 15 YE and IK 227 QE motifs, as being the sumoylation acceptor sites. Using transfection of Ets-1 wildtype (WT) or its sumoylation deficient version (Ets-1 K15R/K227R), as well as WT or mutant proteins of the SUMO pathway, we further demonstrated that the E2 SUMO-conjugating enzyme Ubc9 and a E3 SUMO ligase, PIASy, can enhance Ets-1 sumoylation, while a SUMO protease, SENP1, can desumoylate Ets-1. We also found that Ets-1 is modified by K48-linked polyubiquitinylation independently of the sumoylation acceptor sites and is degraded through the 26S proteasome pathway, while sumoylation of Ets-1 does not affect its stability. Finally, sumoylation of Ets-1 leads to reduced transactivation and we demonstrated that previously identified critical lysine residues in Synergistic Control motifs are the sumoylation acceptor sites of Ets-1. These data show that Ets-1 can be modified by sumoylation and/or ubiquitinylation, with sumoylation repressing transcriptional activity of Ets-1 and having no clear antagonistic action on the ubiquitin-proteasome degradation pathway.

show abstract

Section: Discussionmentioning

confidence: 74%

Regulation of the Ets-1 transcription factor by sumoylation and ubiquitinylation

Degerny

Vintonenko

et al. 2006

Oncogene

View full text Add to dashboard Cite

show abstract

“…As ubiquitination occurs in the C-terminal region of pRb, which is heavily modified by other post-translational modifications (Figure 1), it is possible that interplay exists between ubiquitination and other modifications such as phosphorylation, acetylation and methylation. SUMO (small ubiquitin-related modifier) is a reversible post-translational modification, and many of its protein targets include transcriptional regulators (Muller et al, 2001(Muller et al, , 2004Wilkinson and Henley, 2010). pRb is SUMOylated in the B domain of the pocket region on K720 (Ledl et al, 2005) (Figure 1), within a cluster of lysine residues that are essential for the interaction with LXCXE motif-containing proteins (Chan et al, 2001b).…”

Section: Other Prb Post-translational Modificationsmentioning

confidence: 99%

Diversity within the pRb pathway: is there a code of conduct?

2012

View full text Add to dashboard Cite

The failure of cell proliferation to be properly regulated is a hallmark of tumourigenesis. The retinoblastoma protein (pRb) pathway represents a key component in the regulation of the cell cycle and tumour suppression. Recent findings have revealed new levels of complexity reflecting a repertoire of post-translational modifications that occur on pRb together with its key effector E2F-1. Here we provide an overview of the modifications and consider the possibility of a 'code' that endows pRb with the ability to function in diverse physiological settings.

show abstract

“…In fact, the same lysine residues are acetylated by histone acetyl transferases (HATs) which result in p53 stabilization and activation. [43][44][45] Finally, there are data that neddylation, 44 methylation, 46 and sumoylation (reviewed in Muller et al 47 ) of the CTD can regulate p53 functions.…”

Section: The P53 C-terminal Dna-binding Domainmentioning

confidence: 99%

Transcriptional regulation by p53: one protein, many possibilities

2006

View full text Add to dashboard Cite

The p53 tumor suppressor protein is a DNA sequence-specific transcriptional regulator that, in response to various forms of cellular stress, controls the expression of numerous genes involved in cellular outcomes including among others, cell cycle arrest and cell death. Two key features of the p53 protein are required for its transcriptional activities: its ability to recognize and bind specific DNA sequences and to recruit both general and specialized transcriptional co-regulators. In fact, multiple interactions with co-activators and corepressors as well as with the components of the general transcriptional machinery allow p53 to either promote or inhibit transcription of different target genes. This review focuses on some of the salient features of the interactions of p53 with DNA and with factors that regulate transcription. We discuss as well the complexities of the functional domains of p53 with respect to these interactions.

show abstract

SUMO: a regulator of gene expression and genome integrity

Cited by 257 publications

References 124 publications

Regulation of the Ets-1 transcription factor by sumoylation and ubiquitinylation

Regulation of the Ets-1 transcription factor by sumoylation and ubiquitinylation

Diversity within the pRb pathway: is there a code of conduct?

Transcriptional regulation by p53: one protein, many possibilities

Contact Info

Product

Resources

About