Abstract
PML is a tumor suppressor implicated in leukemia and cancer pathogenesis. PML epitomizes a multiprotein nuclear structure, the PML-nuclear body (PML-NB), whose proper formation and function depends on PML. Studies in knockout (KO) mice and cells unraveled an essential pleiotropic role for PML in multiple p53-dependent and -independent apoptotic pathways. As a result, Pml−/− mice and cells are protected from apoptosis triggered by a number of stimuli such as ionizing radiation, interferon, ceramide, Fas and TNF. It is becoming apparent that PML and the PML-NB act as molecular hubs for the induction and/or reinforcement of programmed cell death through a selective and dynamic regulation of proapoptotic transcriptional events. In addition, recent observations propose a role for PML in checkpoint responses upon DNA damage. Moreover, PML and the PML-NB have also been implicated in the control of genomic stability and DNA repair. Here, we will discuss the molecular mechanisms by which PML regulates these processes and the implication of these findings for cancer pathogenesis and therapy.
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Acknowledgements
We would like to thank members of the laboratory of Molecular and Developmental Biology (MADB) lab at the Memorial Sloan-Kettering Cancer Center for useful discussions. R.B. was a recipient of a T32 training grant from the NIH. This work was supported by the NCI, the De Witt Wallace Fund for Memorial Sloan-Kettering Cancer Center, the MMHCC and NIH Grants to P.P.P.
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Bernardi, R., Pandolfi, P. Role of PML and the PML-nuclear body in the control of programmed cell death. Oncogene 22, 9048–9057 (2003). https://doi.org/10.1038/sj.onc.1207106
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DOI: https://doi.org/10.1038/sj.onc.1207106
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