| Budget Amount *help |
¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Outline of Final Research Achievements |
PCTAIRE1/CDK16/PCTK1 is a distant relative of the cyclin-dependent kinase family that has been implicated in spermatogenesis and neuron development. The function of PCTAIRE1 in tumorigenesis, however, has not been clarified. In prostate, breast, cervical cancer and melanoma cell lines, gene knockdown of PCTAIRE1 using siRNA or shRNA diminished cancer cell proliferation, causing aberrant mitosis with defects in centrosome dynamics. Yeast two-hybrid cDNA library screening identified tumor suppressor p27 as a PCTAIRE1 interactor, and in vitro kinase assays showed PCTAIRE1 phosphorylates p27 at Ser10. Moreover, knockdown of p27 rescued PCTAIRE1knockdown cells from mitotic arrest. Clinically, in primary tumors from patients with breast or prostate cancers, PCTAIRE1 was highly expressed in malignant lesions compared to adjacent normal epithelial tissues. Our findings reveal an unexpected role for PCTAIRE1 in regulating p27 stability, mitosis and tumor growth.
|
