Nuclear and unclear functions of SUMO

Seeler, Jacob-S.; Dejean, Anne

doi:10.1038/nrm1200

Cited by 626 publications

(636 citation statements)

References 128 publications

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“…In the present study, we have demonstrated that endogenous PIASy acts as a negative Recent accumulated studies have demonstrated that many proteins involved in cell-cycle regulation, proliferation, apoptosis and DNA repair are targets for sumoylation, and indicated that alterations in sumoylation could ultimately have impacts on cell growth, cancer development and drug responsiveness [9,25]. Therefore, regulation of sumoylation is tightly linked to homeostasis, and dysregulation of sumoylation may play significant roles in pathological disorders.…”

Section: Discussionsupporting

confidence: 50%

Sumoylation of Smad3 stimulates its nuclear export during PIASy-mediated suppression of TGF-β signaling

Imoto

Ohbayashi

Ikeda

et al. 2008

Biochemical and Biophysical Research Communications

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Sma-and MAD-related protein 3 (Smad3) plays crucial roles in the transforming growth factor-b (TGF-b)-meditaed signaling pathway, which produce a variety of cellular responses, including cell proliferation and differentiation. In our previous study, we demonstrated that protein inhibitor of activated STATy (PIASy) suppresses TGF-b signaling by interacting with and sumoylating Smad3. In the present study, we examined the molecular mechanisms of

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Section: Discussionsupporting

confidence: 50%

Sumoylation of Smad3 stimulates its nuclear export during PIASy-mediated suppression of TGF-β signaling

Imoto

Ohbayashi

Ikeda

et al. 2008

Biochemical and Biophysical Research Communications

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“…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

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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.

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“…Our studies show that UV-induced TIP60 sumoylation is correlated with p53 accumulation in the NB, raising the possibility that TIP60-p53 orchestrates the activity in NB. It has been suggested that the NB is involved in chromatin remodeling (Seeler and Dejean, 2003). TIP60, as a HAT, is an important chromatin modifier to regulate chromatin transcription (Kimura and Horikoshi, 1998).…”

Section: Discussionmentioning

confidence: 99%

Functional characterization of TIP60 sumoylation in UV-irradiated DNA damage response

Cheng

Ke²,

Ding

et al. 2007

Oncogene

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The histone acetyltransferase TIP60 regulates the DNA damage response following genotoxic stress by acetylating histone and remodeling chromatin. However, the molecular mechanisms underlying the TIP60-dependent response to UV-induced DNA damage remain poorly understood. To systematically analyse proteins that regulate TIP60 activity in response to UV irradiation, we performed a proteomic analysis of proteins selectively bound to TIP60 in response to UV irradiation using mass spectrometry and identified a novel regulatory mechanism by which TIP60 orchestrates transcriptional activation of p53-dependent checkpoint response in UV-irradiated cells. The initial step of this pathway involves UV-induced association of TIP60 with SUMO-conjugation enzymes and site-specific sumoylation of TIP60 at lysines 430 and 451 via Ubc9. This sumoylation initiates the relocation of TIP60 from nucleoplasm to the promyelocytic leukemia body, which is essential for the UV-irradiated DNA damage repair response via a p53-dependent pathway. Significantly, inhibition of TIP60 sumoylation by overexpression of non-sumoylatable mutant abrogates the p53-dependent DNA damage response, demonstrating the importance of TIP60 sumoylation in response to UV irradiation. Our biochemical characterization demonstrated that the sumoylation of TIP60 augments its acetyltransferase activity in vitro and in vivo. Thus, this study shed new light on the function and regulation of TIP60 activity in UV-irradiated DNA damage response.

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Nuclear and unclear functions of SUMO

Cited by 626 publications

References 128 publications

Sumoylation of Smad3 stimulates its nuclear export during PIASy-mediated suppression of TGF-β signaling

Sumoylation of Smad3 stimulates its nuclear export during PIASy-mediated suppression of TGF-β signaling

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

Functional characterization of TIP60 sumoylation in UV-irradiated DNA damage response

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