Mitosis-specific phosphorylation of PML at T409 regulates spindle checkpoint.
During mitosis, Promyelocytic leukemia nuclear bodies (PML NBs) change dramatically in morphology and composition, but little is known about function of PML in mitosis. Here, we show that PML is phosphorylated at T409 (PML p409) in a mitosis-specific manner. More importantly, PML p409 contributes to maintain the duration of pro-metaphase and regulates spindle checkpoint. Deficient PML p409 caused a shortening of pro-metaphase and challenged the nocodazole-triggered mitotic arrest. T409A mutation led to a higher frequency of misaligned chromosomes on metaphase plate, and subsequently death in late mitosis. In addition, inhibition of PML p409 repressed growth of tumor cells, suggesting that PML p409 is a potential target for cancer therapy. Collectively, our study demonstrated an important phosphorylated site of PML, which contributed to explore the role of PML in mitosis.
Harbin Medical University Department of Biochemistry and Molecular Biology Harbin China einfachjjf@aliyun.com.
J
J
Jin
Beijing Institute of Radiation Medicine Department of Biochemistry and Molecular Biology Beijing China.
J
J
Liu
D000595:Amino Acid Sequence; D000906:Antibodies / Q000378:metabolism; D000918:Antibody Specificity; D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation; D000939:Epitopes / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D013058:Mass Spectrometry; D008938:Mitosis; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein / Q000737:chemistry / Q000378:metabolism*; D000072417:Protein Domains; D008941:Spindle Apparatus / Q000378:metabolism*
D000906:Antibodies; D000939:Epitopes; D000071156:Promyelocytic Leukemia Protein; D010769:Phosphothreonine; C070576:PML protein, human