The transcriptional role of PML and the nuclear body

Zhong, Sue; Salomoni, Paolo; Pandolfi, Pier Paolo

doi:10.1038/35010583

Cited by 520 publications

(492 citation statements)

References 84 publications

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“…The SAM domain of PcG proteins mediates the interaction with UBC-9, leading to sumoylation, and directs the formation of subnuclear bodies whose characteristics are correlated with physiological function. Sumoylation itself has a variety of effects on its targets in cultured cells, including regulating the subnuclear localization of PML, HIPK2 and TEL [14][15][16] and modulating the transactivational activity of Sp3 and LEF1 (refs. 6,17).…”

Section: Sop-2(ph Sammentioning

confidence: 99%

SUMO modification is required for in vivo Hox gene regulation by the Caenorhabditis elegans Polycomb group protein SOP-2

et al. 2004

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Figure 1Interaction of SOP-2 with UBC-9 and sumoylation. (a) Results of yeast two-hybrid screens using the C terminus of SOP-2 as bait. The strength of the protein interaction is graded on the basis of comparison with controls: human Rb and E2F-1 interaction (+, faint blue color after 24 h in X-gal assay) and rat c-Fos and mouse c-Jun interaction (+++, blue color within 1 h in X-gal assay). (b) Interaction of the wild-type SOP-2 SAM domain with itself, with the SOP-2(bx91) mutant protein and with UBC-9. The bx91 mutation substantially reduces its interaction with UBC-9 but not with the wild-type SOP-2 SAM domain. (c) In vitro and in vivo sumoylation of SOP-2. In vitro sumoylation was carried out using labeled SOP-2 and purified sumoylation components. In vivo sumoylation of hemagglutinin-tagged SOP-2 and the SOP-2(bx91) mutant was done after transfection and expression in mammalian U2OS cells. Cell lysates were analyzed by immunoprecipitation (IP) with antibody to SUMO and western blotting with antibody to hemagglutinin.

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Section: Sop-2(ph Sammentioning

confidence: 99%

SUMO modification is required for in vivo Hox gene regulation by the Caenorhabditis elegans Polycomb group protein SOP-2

et al. 2004

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“…The PML protein has first been described as the causal agent in acute promyelocytic leukaemia as a fusion with the RARa receptor generated by the chromosomal translocation t(15;17) (Ascoli and Maul, 1991;de The et al, 1991;Kakizuka et al, 1991;Chang et al, 1992;Goddard et al, 1992;Kastner et al, 1992;Pandolfi et al, 1992;Dyck et al, 1994;Koken et al, 1994;Weis et al, 1994;Melnick and Licht, 1999;. Since these initial findings, it has become evident that PML is a general tumour suppressor frequently deregulated in various tumour types (Gurrieri et al, 2004) most presumably involving secondary effects of PML bodies as sites of protein degradation (Lallemand-Breitenbach et al, 2001), transcriptional regulation (Li et al, 2000;Zhong et al, 2000), cellular senescence (Ferbeyre et al, 2000;Pearson et al, 2000;Bischof et al, 2002;Langley et al, 2002), tumour suppression (Salomoni and Pandolfi, 2002;Salomoni et al, 2008), DNA repair (Bischof et al, 2001;Carbone et al, 2002), apoptosis (Hofmann and Will, 2003;Takahashi et al, 2004) and epigenetic regulation (Torok et al, 2009). Interestingly, functional inactivation of the E1B-55K leucine-rich nuclear export sequence (NES) induces enhanced posttranslational modification of E1B-55K by the small ubiquitin-related modifier 1 (SUMO1) at lysine 104 (SUMO-conjugation motif, SCM) as well as augments transformation of primary rat cells involving the accumulation of p53, E1B-55K and PML in subnuclear aggregates (Endter et al, 2001(Endter et al, , 2005.…”

Section: Introductionmentioning

confidence: 99%

SUMO modification of E1B-55K oncoprotein regulates isoform-specific binding to the tumour suppressor protein PML

Wimmer

Schreiner

Everett³

et al. 2010

Oncogene

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The E1B-55K product from human adenovirus is a substrate of the small ubiquitin-related modifier (SUMO)-conjugation system. SUMOylation of E1B-55K is required to transform primary mammalian cells in cooperation with adenovirus E1A and to repress p53 tumour suppressor functions. The biochemical consequences of SUMO1 conjugation of 55K have so far remained elusive. Here, we report that E1B-55K physically interacts with different isoforms of the tumour suppressor protein promyelocytic leukaemia (PML). We show that E1B-55K binds to PML isoforms IV and V in a SUMO1-dependent and -independent manner. Interaction with PML-IV promotes the localization of 55K to PMLcontaining subnuclear structures (PML-NBs). In virusinfected cells, this process is negatively regulated by other viral proteins, indicating that binding to PML is controlled through reversible SUMOylation in a timely coordinated manner. These results together with earlier work are consistent with the idea that SUMOylation regulates targeting of E1B-55K to PML-NBs, known to control transcriptional regulation, tumour suppression, DNA repair and apoptosis. Furthermore, they suggest that SUMO1-dependent modulation of p53-dependent growth suppression through E1B-55K PML-IV interaction has a key role in adenovirus-mediated cell transformation.

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“…[3][4][5][6][7] Besides a number of viral proteins, to date more than 40 different cellular proteins have been found in association with PML-NBs ( Figure 1). Although the molecular function of PMLNBs is currently not clear, there is accumulating evidence that PML-NBs are regulatory domains involved in various biological processes, including protein degradation, 5 transcriptional regulation, 8,9 cell growth, 10,11 antiviral response, 12,13 cellular senescence, [14][15][16][17] tumour suppression, 18 DNA repair 19,20 and apoptosis. [21][22][23][24][25] However, how can one explain that so many different and unrelated processes are linked to these nuclear domains?…”

Section: Introductionmentioning

confidence: 99%

Body language: the function of PML nuclear bodies in apoptosis regulation

2003

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Promyelocytic leukaemia (PML) nuclear bodies (NBs) are macromolecular nuclear domains present in virtually every mammalian cell. PML nuclear bodies (PML-NBs) were functionally linked to various fundamental cellular processes, including transcriptional control, tumour suppression and apoptosis regulation. Supporting the important function of PML and its associated NBs in apoptosis regulation, several apoptotic regulators localise to PML-NBs, and cells from PMLdeficient mice show severe apoptotic defects, including induction of genotoxic stress and death receptor CD95 (Fas/ APO-1) activation. Based on the current literature, we hypothesise that PML-NBs regulate apoptosis through different molecular mechanisms, on the one hand by acting as macromolecular scaffolds for recruitment and post-translational modification of the apoptotic key regulator p53, and on the other by regulating the subcellular bioavailability and quality of some apoptotic signal transducers.

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The transcriptional role of PML and the nuclear body

Cited by 520 publications

References 84 publications

SUMO modification is required for in vivo Hox gene regulation by the Caenorhabditis elegans Polycomb group protein SOP-2

SUMO modification is required for in vivo Hox gene regulation by the Caenorhabditis elegans Polycomb group protein SOP-2

SUMO modification of E1B-55K oncoprotein regulates isoform-specific binding to the tumour suppressor protein PML

Body language: the function of PML nuclear bodies in apoptosis regulation

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