ArticleMolecular and cellular biology2003
PML colocalizes with and stabilizes the DNA damage response protein TopBP1.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
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- On the Prevalence and Roles of Proteins Undergoing Liquid-Liquid Phase Separation in the Biogenesis of PML-Bodies.Biomolecules · 2023Article
- Review
- CK2 kinase-mediated PHF8 phosphorylation controls TopBP1 stability to regulate DNA replication.Nucleic acids research · 2020Article
- Nuclear body phase separation drives telomere clustering in ALT cancer cells.Molecular biology of the cell · 2020Article
- Synthetic lethality of cytolytic HSV-1 in cancer cells with ATRX and PML deficiency.Journal of cell science · 2019Article
- PML-like subnuclear bodies, containing XRCC1, juxtaposed to DNA replication-based single-strand breaks.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Importance of Promyelocytic Leukema Protein (PML) for Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication.Frontiers in microbiology · 2018Article
- Myogenic differentiation triggers PML nuclear body loss and DAXX relocalization to chromocentres.Cell death & disease · 2017Article
- PML nuclear body disruption impairs DNA double-strand break sensing and repair in APL.Cell death & disease · 2016Article
- TRAIP/RNF206 is required for recruitment of RAP80 to sites of DNA damage.Nature communications · 2016Article
- Nesprin-2-dependent ERK1/2 compartmentalisation regulates the DNA damage response in vascular smooth muscle cell ageing.Cell death and differentiation · 2015Article
- The functional interactome of PYHIN immune regulators reveals IFIX is a sensor of viral DNA.Molecular systems biology · 2015Article
- The function, regulation and therapeutic implications of the tumor suppressor protein, PML.Cell & bioscience · 2015Review
- The role of post-translational modifications in fine-tuning BLM helicase function during DNA repair.DNA repair · 2014Review
- Importin β-dependent nuclear import of TopBP1 in ATR-Chk1 checkpoint in Xenopus egg extracts.Cellular signalling · 2014Article
- The tumor suppressor PML specifically accumulates at RPA/Rad51-containing DNA damage repair foci but is nonessential for DNA damage-induced fibroblast senescence.Molecular and cellular biology · 2014Article
- PML-mediated signaling and its role in cancer stem cells.Oncogene · 2014Review
- Cellular senescence and protein degradation: breaking down cancer.Cell cycle (Georgetown, Tex.) · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The PML tumor suppressor gene is consistently disrupted by t(15;17) in patients with acute promyelocytic leukemia. Promyelocytic leukemia protein (PML) is a multifunctional protein that plays essential roles in cell growth regulation, apoptosis, transcriptional regulation, and genome stability. Our study here shows that PML colocalizes and associates in vivo with the DNA damage response protein TopBP1 in response to ionizing radiation (IR). Both PML and TopBP1 colocalized with the IR-induced bromodeoxyuridine single-stranded DNA foci. PML and TopBP1 also colocalized with Rad50, Brca1, ATM, Rad9, and BLM. IR and interferon (IFN) coinduce the expression levels of both TopBP1 and PML. In PML-deficient NB4 cells, TopBP1 was unable to form IR-induced foci. All-trans-retinoic acid induced reorganization of the PML nuclear body (NB) and reappearance of the IR-induced TopBP1 foci. Inhibition of PML expression by siRNA is associated with a significant decreased in TopBP1 expression. Furthermore, PML-deficient cells express a low level of TopBP1, and its expression cannot be induced by IR or IFN. Adenovirus-mediated overexpression of PML in PML(-/-) mouse embryo fibroblasts substantially increased TopBP1 expression, which colocalized with the PML NBs. These studies demonstrated a mechanism of PML-dependent expression of TopBP1. PML overexpression induced TopBP1 protein but not the mRNA expression. Pulse-chase labeling analysis demonstrated that PML overexpression stabilized the TopBP1 protein, suggesting that PML plays a role in regulating the stability of TopBP1 in response to IR. Together, our findings demonstrate that PML regulates TopBP1 functions by association and stabilization of the protein in response to IR-induced DNA damage.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.