期刊
FRONTIERS IN ONCOLOGY
卷 2, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2012.00204
关键词
promyelocytic leukemia; PML-RAR alpha; post-translational modifications; protein kinases; ubiquitin E3 ligases
类别
资金
- German Research Foundation [SCHM 1417/7-1, SCHM 1417/8-1, SCHM1417/9-1, SFB/TRR 81]
- PROMISE [IRTG1566]
- German Academic Exchange Service [A/08/98404, A/11/90192]
Post-translat onal modifications (PTMs) regulate multiple biological functions of the promyelocytic leukemia (PML) protein and also the fission, disassembly, and rebuilding of PML nuclear bodies (PML-NBs) during the cell cycle. Pathway-specific PML modification patterns ensure proper signal output from PML-NBs that suit the specific functional requirements. Here we comprehensively review the signaling pathways and enzymes that modify PML and also the oncogenic PML-RAR alpha fusion protein. Many PTMs occur in a hierarchical and timely organized fashion. Phosphorylation or acetylation constitutes typical starting points for many PML modifying events, while degradative ubiquitination is an irreversible end point of the modification cascade. As this hierarchical organization of PTMs frequently turns phosphorylation events as primordial events, kinases or phosphatases regulating PML phosphorylation may be interesting drug targets to manipulate the downstream modifications and thus the stability and function of PML or PML-RAR alpha.
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