PML Bodies in Mitosis

Promyelocytic leukemia (PML) bodies are dynamic intracellular structures that recruit and release a variety of different proteins in response to stress, virus infection, DNA damage and cell cycle progression. While PML bodies primarily are regarded as nuclear compartments, they are forced to travel to the cytoplasm each time a cell divides, due to breakdown of the nuclear membrane at entry into mitosis and subsequent nuclear exclusion of nuclear material at exit from mitosis. Here we review the biochemical and biophysical transitions that occur in PML bodies during mitosis and discuss this in light of post-mitotic nuclear import, cell fate decision and acute promyelocytic leukemia therapy.

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Coordination between Cell Cycle Progression and Cell Fate Decision by the p53 and E2F1 Pathways in Response to DNA Damage

Journal of Biological Chemistry ◽

10.1074/jbc.m110.134650 ◽

2010 ◽

Vol 285 (41) ◽

pp. 31571-31580 ◽

Cited By ~ 36

Author(s):

Xiao-Peng Zhang ◽

Feng Liu ◽

Wei Wang

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Cell Fate ◽

Cell Cycle Progression ◽

Cell Fate Decision ◽

Cycle Progression ◽

Fate Decision

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Deubiquitylation and stabilization of p21 by USP11 is critical for cell-cycle progression and DNA damage responses

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1714938115 ◽

2018 ◽

Vol 115 (18) ◽

pp. 4678-4683 ◽

Cited By ~ 44

Author(s):

Tanggang Deng ◽

Guobei Yan ◽

Xin Song ◽

Lin Xie ◽

Yu Zhou ◽

...

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Cell Fate ◽

Cell Cycle Progression ◽

Kinase Inhibitor ◽

Independent Manner ◽

Cycle Progression ◽

Dna Damage Responses ◽

Fate Decision

p21WAF1/CIP1 is a broad-acting cyclin-dependent kinase inhibitor. Its stability is essential for proper cell-cycle progression and cell fate decision. Ubiquitylation by the multiple E3 ubiquitin ligase complexes is the major regulatory mechanism of p21, which induces p21 degradation. However, it is unclear whether ubiquitylated p21 can be recycled. In this study, we report USP11 as a deubiquitylase of p21. In the nucleus, USP11 binds to p21, catalyzes the removal of polyubiquitin chains conjugated onto p21, and stabilizes p21 protein. As a result, USP11 reverses p21 polyubiquitylation and degradation mediated by SCFSKP2, CRL4CDT2, and APC/CCDC20 in a cell-cycle–independent manner. Loss of USP11 causes the destabilization of p21 and induces the G1/S transition in unperturbed cells. Furthermore, p21 accumulation mediated by DNA damage is completely abolished in cells depleted of USP11, which results in abrogation of the G2 checkpoint and induction of apoptosis. Functionally, USP11-mediated stabilization of p21 inhibits cell proliferation and tumorigenesis in vivo. These findings reveal an important mechanism by which p21 can be stabilized by direct deubiquitylation, and they pinpoint a crucial role of the USP11-p21 axis in regulating cell-cycle progression and DNA damage responses.

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Deubiquitylation and stabilization of p21 by USP11 is critical for cell cycle progression and DNA damage responses

10.1101/172999 ◽

2017 ◽

Author(s):

Tanggang Deng ◽

Guobei Yan ◽

Yu Zhou ◽

Xiaoxiao Hu ◽

Jianglin Li ◽

...

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Cell Fate ◽

Cell Cycle Progression ◽

Kinase Inhibitor ◽

Independent Manner ◽

Cycle Progression ◽

Dna Damage Responses ◽

Fate Decision

Abstractp21WAF1/CIP1is a broad-acting cyclin-dependent kinase inhibitor. Its stability is essential for proper cell cycle progression and cell fate decision. Ubiquitylation by the multiple E3 ubiquitin ligases complex is the major regulatory mechanism of p21, which induces p21 degradation. However, it is unclear whether ubiquitylated p21 can be recycled. In this study, we report USP11 as a deubiquitylase of p21. In the nucleus, USP11 binds to p21, catalyzes the removal of polyubiquitin chains conjugated onto p21 and stabilizes p21 protein. As a result, USP11 reverses p21 polyubiquitylation and degradation mediated by SCFSKP2, CRL4CDT2and APC/CCDT20in a cell cycle-independent manner. Loss of USP11 causes the destabilization of p21 and induces the G1/S transition in unperturbed cells. Furthermore, p21 accumulation mediated by DNA damage is completely abolished in cells depleted of USP11, which results in abrogation of the G2 checkpoint and induction of apoptosis. Functionally, USP11-mediated stabilization of p21 inhibits cell proliferation and tumorigenesis in vivo. These findings reveal an important mechanism by which p21 can be stabilized by direct deubiquitylation and pinpoint a crucial role of the USP11-p21 axis in regulating cell cycle progression and DNA damage responses.

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