2. Academic Validation
  3. Cyclin-dependent kinase 1-mediated phosphorylation of SET at serine 7 is essential for its oncogenic activity

Cyclin-dependent kinase 1-mediated phosphorylation of SET at serine 7 is essential for its oncogenic activity

  • Cell Death Dis. 2019 May 16;10(6):385. doi: 10.1038/s41419-019-1621-2.
Ling Yin 1 2,  Yongji Zeng 2,  Yi Xiao 2 3,  Yuanhong Chen 2,  Hong Shen 1,  Jixin Dong 4
Affiliations

Affiliations

  • 1 Department of Oncology, Xiangya Hospital, Central South University, 410008, Changsha, China.
  • 2 Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
  • 3 Department of Biochemistry and Molecular Biology, Shandong University School of Basic Medical Science, 250012, Jinan, China.
  • 4 Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA. [email protected].
PMID: 31097686 DOI: 10.1038/s41419-019-1621-2
Abstract

SE translocation (SET), an inhibitor of protein Phosphatase 2A (PP2A), plays important roles in Mitosis and possesses oncogenic activity in several types of Cancer. However, little is known regarding its regulation. Here we reveal a novel phosphorylation site of SET isoform 1, and we have determined its biological significance in tumorigenesis. We found that the mitotic kinase cyclin-dependent kinase 1 (CDK1) phosphorylates SET isoform 1 in vitro and in vivo at serine 7 during antitubulin drug-induced mitotic arrest and normal Mitosis. SET deletion resulted in massive multipolar spindles, chromosome misalignment and missegregation, and centrosome amplification during Mitosis. Moreover, mitotic phosphorylation of SET isoform 1 is required for cell migration, invasion, and anchorage-independent growth in vitro and tumorigenesis in xenograft animal models. We further documented that SET phosphorylation affects Akt activity. Collectively, our findings suggest that SET isoform 1 promotes oncogenesis in a mitotic phosphorylation-dependent manner.

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