Contribution of the C-terminal Regions of Promyelocytic Leukemia Protein (PML) Isoforms II and V to PML Nuclear Body Formation

Geng, Yunyun; Monajembashi, Shamci; Shao, Anwen; Cui, Di; He, Wenqi; Chen, Zhongzhou; Hemmerich, Peter; Tang, Jun

doi:10.1074/jbc.m112.374769

Cited by 39 publications

(52 citation statements)

References 58 publications

(7 reference statements)

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“…DAXX also coprecipitates with a transiently expressed EGFP-PML (isoform V) construct (Supplemental Fig. 2F), consistent with a recent study showing that the C terminus of this isoform recruits DAXX into NBs in MEFs (Geng et al 2012). Furthermore, both endogenous H3.3 ( Fig.…”

Section: Resultssupporting

confidence: 72%

DAXX-dependent supply of soluble (H3.3–H4) dimers to PML bodies pending deposition into chromatin

et al. 2012

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Replication-independent chromatin deposition of histone variant H3.3 is mediated by several chaperones. We report a multistep targeting of newly synthesized epitope-tagged H3.3 to chromatin via PML bodies. H3.3 is recruited to PML bodies in a DAXX-dependent manner, a process facilitated by ASF1A. DAXX is required for enrichment of ATRX, but not ASF1A or HIRA, with PML. Nonetheless, the chaperones colocalize with H3.3 at PML bodies and are found in one or more complexes with PML. Both DAXX and PML are necessary to prevent accumulation of a soluble, nonincorporated pool of H3.3. H3.3 targeting to PML is enhanced with an (H3.3-H4) 2 tetramerization mutant of H3.3, suggesting H3.3 recruitment to PML as an (H3.3-H4) dimer rather than as a tetramer. Our data support a model of DAXX-mediated recruitment of (H3.3-H4) dimers to PML bodies, which may function as triage centers for H3.3 deposition into chromatin by distinct chaperones.

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Section: Resultssupporting

confidence: 72%

DAXX-dependent supply of soluble (H3.3–H4) dimers to PML bodies pending deposition into chromatin

et al. 2012

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“…Thus, it is assumed that PML-V represents the major scaffold protein of PML-NBs. [101][102][103] Within our study, we showed for the first time that PML-IV and PML-V Figure 6. PML-IV/-V-binding affects E1B-55K-dependent p53 subcellular localization.…”

Section: Discussionmentioning

confidence: 89%

PML isoforms IV and V contribute to adenovirus-mediated oncogenic transformation by functionally inhibiting the tumor-suppressor p53

et al. 2015

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Although modulation of the cellular tumor-suppressor p53 is considered to have the major role in E1A/E1B-55K-mediated tumorigenesis, other promyelocytic leukemia nuclear body (PML-NB)/PML oncogenic domain (POD)-associated factors including SUMO, Mre11, Daxx, as well as the integrity of these nuclear bodies contribute to the transformation process. However, the biochemical consequences and oncogenic alterations of PML-associated E1B-55K by SUMO-dependent PML-IV and PML-V interaction have so far remained elusive. We performed mutational analysis to define a PML interaction motif within the E1B-55K polypeptide. Our results showed that E1B-55K/PML binding is not required for p53, Mre11 and Daxx interaction. We also observed that E1B-55K lacking subnuclear PML localization because of either PML-IV or PML-V-binding deficiency was no longer capable of mediating E1B-55K-dependent SUMOylation of p53, inhibition of p53-mediated transactivation or efficiently transforming primary rodent cells. These results together with the observation that E1B-55K-dependent SUMOylation of p53 is required for efficient cell transformation, provides evidence for the idea that the SUMO ligase activity of the E1B-55K viral oncoprotein is intimately linked to its growth-promoting oncogenic activities.

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“…In human, there are seven splice variants of PML and all of them perform a variety of distinct functions [7]. Recently, it has been demonstrated that PML variant II is one of the most abundant and plays a key role in regulating the function and structure of PML-NBs [11]. In this study, we have used comparative proteomics to elucidate all the proteins that are differentially expressed in MEFs that are incapable of expressing PML [12].…”

Section: Introductionmentioning

confidence: 99%

Promyelocytic Leukemia (PML) Protein Plays Important Roles in Regulating Cell Adhesion, Morphology, Proliferation and Migration

et al. 2013

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PML protein plays important roles in regulating cellular homeostasis. It forms PML nuclear bodies (PML-NBs) that act like nuclear relay stations and participate in many cellular functions. In this study, we have examined the proteome of mouse embryonic fibroblasts (MEFs) derived from normal (PML+/+) and PML knockout (PML−/−) mice. The aim was to identify proteins that were differentially expressed when MEFs were incapable of producing PML. Using comparative proteomics, total protein were extracted from PML−/− and PML+/+ MEFs, resolved by two dimensional electrophoresis (2-DE) gels and the differentially expressed proteins identified by LC-ESI-MS/MS. Nine proteins (PML, NDRG1, CACYBP, CFL1, RSU1, TRIO, CTRO, ANXA4 and UBE2M) were determined to be down-regulated in PML−/− MEFs. In contrast, ten proteins (CIAPIN1, FAM50A, SUMO2 HSPB1 NSFL1C, PCBP2, YWHAG, STMN1, TPD52L2 and PDAP1) were found up-regulated. Many of these differentially expressed proteins play crucial roles in cell adhesion, migration, morphology and cytokinesis. The protein profiles explain why PML−/− and PML+/+ MEFs were morphologically different. In addition, we demonstrated PML−/− MEFs were less adhesive, proliferated more extensively and migrated significantly slower than PML+/+ MEFs. NDRG1, a protein that was down-regulated in PML−/− MEFs, was selected for further investigation. We determined that silencing NDRG1expression in PML+/+ MEFs increased cell proliferation and inhibited PML expression. Since NDRG expression was suppressed in PML−/− MEFs, this may explain why these cells proliferate more extensively than PML+/+ MEFs. Furthermore, silencing NDRG1expression also impaired TGF-β1 signaling by inhibiting SMAD3 phosphorylation.

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Contribution of the C-terminal Regions of Promyelocytic Leukemia Protein (PML) Isoforms II and V to PML Nuclear Body Formation

Cited by 39 publications

References 58 publications

DAXX-dependent supply of soluble (H3.3–H4) dimers to PML bodies pending deposition into chromatin

DAXX-dependent supply of soluble (H3.3–H4) dimers to PML bodies pending deposition into chromatin

PML isoforms IV and V contribute to adenovirus-mediated oncogenic transformation by functionally inhibiting the tumor-suppressor p53

Promyelocytic Leukemia (PML) Protein Plays Important Roles in Regulating Cell Adhesion, Morphology, Proliferation and Migration

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