Stabilization of PML nuclear localization by conjugation and oligomerization of SUMO-3

Fu, Chuanhai; Ahmed, Kashif; Ding, Husheng; Ding, Xia; Lan, Jianping; Yang, Zhihong; Miao, Yong; Zhu, Yuanyuan; Shi, Yunyu; Zhu, Jingjing; Huang, He; Yao, Xuebiao

doi:10.1038/sj.onc.1208714

Cited by 108 publications

(79 citation statements)

References 31 publications

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“…Sumoylation initiates the relocation of TIP60 to the PML body Previous studies show that protein sumoylation plays an important role in relocation of nuclear proteins such as PML (for example, Fu et al, 2005). To evaluate the impact of sumoylation on TIP60 distribution, HeLa cells were transfected with GFP-TIP60 and assessed for its subcellular localization.…”

Section: Uv Irradiation Induces the Sumoylation Of Tip60 At Lysines 4mentioning

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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Section: Uv Irradiation Induces the Sumoylation Of Tip60 At Lysines 4mentioning

confidence: 99%

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

Cheng

Ke²,

Ding

et al. 2007

Oncogene

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“…This result is also in line with previous work of other groups demonstrating that PML is modified by SUMO-1, and that SUMOylation of PML is essential for the recruitment of other proteins to PML NBs (15)(16)(17). Although recent data suggest that in addition to SUMO-1 other members of the SUMO family such as SUMO-3 are also capable of modifying PML, the role of these SUMOs appears to be distinct in that SUMO-3 is responsible primarily for stabilizing the nuclear localization of PML (18). Of interest, increased levels of SUMO-1 in RA SFs resulted in a more pronounced formation of PML NBs, suggesting that the differences in the expression of SUMO-1 between RA and OA SFs have functional consequences.…”

Section: A Upper and B Upper)mentioning

confidence: 90%

Modification of nuclear PML protein by SUMO-1 regulates Fas-induced apoptosis in rheumatoid arthritis synovial fibroblasts

Meinecke

Cinski

Baier

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

124

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The small ubiquitin-like modifier (SUMO)-1 is an important posttranslational regulator of different signaling pathways and involved in the formation of promyelocytic leukemia (PML) protein nuclear bodies (NBs). Overexpression of SUMO-1 has been associated with alterations in apoptosis, but the underlying mechanisms and their relevance for human diseases are not clear. Here, we show that the increased expression of SUMO-1 in rheumatoid arthritis (RA) synovial fibroblasts (SFs) contributes to the resistance of these cells against Fas-induced apoptosis through increased SUMOylation of nuclear PML protein and increased recruitment of the transcriptional repressor DAXX to PML NBs. We also show that the nuclear SUMO-protease SENP1, which is found at lower levels in RA SFs, can revert the apoptosis-inhibiting effects of SUMO-1 by releasing DAXX from PML NBs. Our findings indicate that in RA SFs overexpression of SENP1 can alter the SUMO-1-mediated recruitment of DAXX to PML NBs, thus influencing the proapoptotic effects of DAXX. Accumulation of DAXX in PML NBs by SUMO-1 may, therefore, contribute to the pathogenesis of inflammatory disorders.inflammation ͉ autoimmunity ͉ DAXX ͉ SENP

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“…14 A SIM has been found in TTRAP sequence, and TTRAP can bind SUMO-2/3 with a higher affinity than SUMO-1. 6 As PML itself can be SUMOylated by SUMO-3, 15 we asked whether TTRAP SIM domain might have a role in recognition of PML and in PML-mediated TTRAP recruitment to nucleolar cavities. To address this issue, we generated a TTRAP SIM mutant unable to recognize SUMO-2/3 moieties.…”

Section: Resultsmentioning

confidence: 99%

The PML nuclear bodies-associated protein TTRAP regulates ribosome biogenesis in nucleolar cavities upon proteasome inhibition

et al. 2011

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TRAF and TNF receptor-associated protein (TTRAP) is a multifunctional protein that can act in the nucleus as a 5 0 -tyrosyl DNA phosphodiesterase and in the cytoplasm as a regulator of cell signaling. In this paper we show that in response to proteasome inhibition TTRAP accumulates in nucleolar cavities in a promyelocytic leukemia protein-dependent manner. In the nucleolus, TTRAP contributes to control levels of ribosomal RNA precursor and processing intermediates, and this phenotype is independent from its 5 0 -tyrosyl DNA phosphodiesterase activity. Our findings suggest a previously unidentified function for TTRAP and nucleolar cavities in ribosome biogenesis under stress. Cell Death and Differentiation (2012) 19, 488-500; doi:10.1038/cdd.2011; published online 16 September 2011 TRAF and TNF receptor-associated protein (TTRAP) is a 5 0 -tyrosyl DNA phosphodiesterase that is required for the repair of topoisomerase2-induced DNA double-strand breaks. 1 It is a member of the endonuclease/exonuclease/ phosphatase family of proteins containing an Mg(2 þ )-dependent apurinic/apyrimidinic endonuclease Ape1-like domain. 2 Various yeast-two hybrid (Y2H) screenings and functional studies have unveiled TTRAP ability to interact with TNF receptors (TNFR) family members and TNFR-associated factors (TRAFs), especially TRAF6. 3 Furthermore, TTRAP was isolated as ETS-associated protein II 4 and as alk4-and smad3-binding protein. 5 Interestingly, TTRAP sequence contains a SUMO-interacting motif (SIM) that is required for its high affinity binding to SUMO-2/3. 6 TTRAP may thus has a role in the cytoplasm as a signaling molecule and in the nucleus as a DNA damage response protein and transcriptional regulator. In this context, its potential interaction with promyelocytic leukemia protein (PML), as previously determined in Y2H, suggests that TTRAP is a PML nuclear bodies (PML-NBs)-associated protein. 7 It remains unclear whether its 5 0 -tyrosyl DNA phosphodiesterase activity may account for all TTRAP biological functions.According to the cellular context, TTRAP may either protect cells from apoptosis or promote death. [8][9][10] When human SH-SY5Y cells are stressed by low doses of proteasome inhibitors, TTRAP is neuroprotective. In these conditions, endogenous TTRAP relocalizes to the cytoplasm and forms aggresome-like inclusions.In this paper we show that in response to high doses of proteasome inhibitors, TTRAP localizes to the nucleolus. This accumulation requires the association to PML-NBs and occurs in nucleolar cavities, a compartment devoid of markers of the 'ribosomal nucleolus'. Lack of TTRAP alters the levels of precursor ribosomal RNA (pre-rRNA) and processing intermediates, suggesting a new role of the PML-NBs-associated protein TTRAP in rRNA biogenesis. This function is dependent on TTRAP SIM motif, but is independent from its 5 0 -tyrosyl DNA phosphodiesterase activity. Altogether, these data suggest a novel function for TTRAP and nucleolar cavities in controlling rRNA biogenesis in response to proteasome inhibiti...

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Stabilization of PML nuclear localization by conjugation and oligomerization of SUMO-3

Cited by 108 publications

References 31 publications

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

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

Modification of nuclear PML protein by SUMO-1 regulates Fas-induced apoptosis in rheumatoid arthritis synovial fibroblasts

The PML nuclear bodies-associated protein TTRAP regulates ribosome biogenesis in nucleolar cavities upon proteasome inhibition

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