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

Hofmann, Thomas G.; Will, Hans

doi:10.1038/sj.cdd.4401313

Cited by 99 publications

(112 citation statements)

References 148 publications

(174 reference statements)

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“…PML and PML NBs are implicated in apoptosis (2,19,42) and antiviral responses (33). This may explain why PML NBs are preferential targets of viral infection.…”

Section: Discussionmentioning

confidence: 99%

Cross Talk between PML and p53 during Poliovirus Infection: Implications for Antiviral Defense

Pampin

Simonin

Blondel

et al. 2006

J Virol

105

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PML nuclear bodies (NBs) are dynamic intranuclear structures harboring numerous transiently or permanently localized proteins. PML, the NBs' organizer, is directly induced by interferon, and its expression is critical for antiviral host defense. We describe herein the molecular events following poliovirus infection that lead to PML-dependent p53 activation and protection against virus infection. Poliovirus infection induces PML phosphorylation through the extracellular signal-regulated kinase pathway, increases PML SUMOylation, and induces its transfer from the nucleoplasm to the nuclear matrix. These events result in the recruitment of p53 to PML NBs, p53 phosphorylation on Ser15, and activation of p53 target genes leading to the induction of apoptosis. Moreover, the knock-down of p53 by small interfering RNA results in higher poliovirus replication, suggesting that p53 participates in antiviral defense. This effect, which requires the presence of PML, is transient since poliovirus targets p53 by inducing its degradation in a proteasome-and MDM2-dependent manner. Our results provide evidence of how poliovirus counteracts p53 antiviral activity by regulating PML and NBs, thus leading to p53 degradation.

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“…PML and PML NBs are implicated in apoptosis (2,19,42) and antiviral responses (33). This may explain why PML NBs are preferential targets of viral infection.…”

Section: Discussionmentioning

confidence: 99%

Cross Talk between PML and p53 during Poliovirus Infection: Implications for Antiviral Defense

Pampin

Simonin

Blondel

et al. 2006

J Virol

105

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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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“…5 g and h, these experiments clearly demonstrated an increased association of DAXX with FADD after liberation from the PML NBs in RA SFs. Discussion SUMO-1 acts as a posttranslational regulator of different signaling pathways and is involved in the formation of PML NBs (12,13). Overexpression of SUMO-1 has been associated with alterations in apoptosis (7), but the mechanisms that mediate these effects and particularly their relevance for disease conditions are unclear.…”

Section: A Upper and B Upper)mentioning

confidence: 99%

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.

122

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

Cited by 99 publications

References 148 publications

Cross Talk between PML and p53 during Poliovirus Infection: Implications for Antiviral Defense

Cross Talk between PML and p53 during Poliovirus Infection: Implications for Antiviral Defense

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

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

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