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Melnick, A. & Licht, J. D. Deconstructing a disease: RARα, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood 93, 3167-3215 (1999). This review on the molecular pathogenesis of APL is a classic. Although some aspects are perhaps outdated, it still provides a broad and detailed description of the functions of the fusion partners of RARα.
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PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1
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Dror, N. et al. Interferon regulatory factor-8 is indispensable for the expression of promyelocytic leukemia and the formation of nuclear bodies in myeloid cells. J. Biol. Chem. 282, 5633-5640 (2007). This paper shows that a loss of expression of IRF8 in human CML correlates with a loss of expression of PML. This is also the first report to demonstrate that loss of expression of PML can be detected in leukaemias in addition to solid tumours.
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Dror, N. et al. Interferon regulatory factor-8 is indispensable for the expression of promyelocytic leukemia and the formation of nuclear bodies in myeloid cells. J. Biol. Chem. 282, 5633-5640 (2007). This paper shows that a loss of expression of IRF8 in human CML correlates with a loss of expression of PML. This is also the first report to demonstrate that loss of expression of PML can be detected in leukaemias in addition to solid tumours.
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34
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Altered distribution of the promyelocytic leukemia-associated protein is associated with cellular senescence
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Ferbeyre, G. et al. PML is induced by oncogenic ras and promotes premature senescence. Genes Dev. 14, 2015-2027 (2000). References 35 and 36 are the first reports that implicate PML-NBs in the regulation of cellular senescence. They show that PML-NBs increase in size and number following the induction of senescence and that PML regulates p53 acetylation and activation.
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Ferbeyre, G. et al. PML is induced by oncogenic ras and promotes premature senescence. Genes Dev. 14, 2015-2027 (2000). References 35 and 36 are the first reports that implicate PML-NBs in the regulation of cellular senescence. They show that PML-NBs increase in size and number following the induction of senescence and that PML regulates p53 acetylation and activation.
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37
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PML is a direct p53 target that modulates p53 effector functions
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Nacerddine, K. et al. The SUMO pathway is essential for nuclear integrity and chromosome segregation in mice. Dev. Cell 9, 769-779 (2005). Describes the generation of mice that are deficient for the SUMO E2-conjugating enzyme UBC9. Loss of UBC9 leads to early embryonic lethality and major defects in chromosome condensation and segregation. Moreover, PML-NBs are disrupted along with other nuclear structures.
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Nacerddine, K. et al. The SUMO pathway is essential for nuclear integrity and chromosome segregation in mice. Dev. Cell 9, 769-779 (2005). Describes the generation of mice that are deficient for the SUMO E2-conjugating enzyme UBC9. Loss of UBC9 leads to early embryonic lethality and major defects in chromosome condensation and segregation. Moreover, PML-NBs are disrupted along with other nuclear structures.
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Shen, T. H., Lin, H. K., Scaglioni, P. P., Yung, T. M. & Pandolfi, P. P. The mechanisms of PML-nuclear body formation. Mol. Cell 24, 331-339 (2006). PML is shown to have a SUMO-binding domain that is necessary for PML-NB formation. A model for the nucleation of PML-NBs is presented.
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Shen, T. H., Lin, H. K., Scaglioni, P. P., Yung, T. M. & Pandolfi, P. P. The mechanisms of PML-nuclear body formation. Mol. Cell 24, 331-339 (2006). PML is shown to have a SUMO-binding domain that is necessary for PML-NB formation. A model for the nucleation of PML-NBs is presented.
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