APC-CCdh1 Targets Brain-Specific Kinase 2 BRSK2 for Degradation via the Ubiquitin-Proteasome PathwayReport as inadecuate




APC-CCdh1 Targets Brain-Specific Kinase 2 BRSK2 for Degradation via the Ubiquitin-Proteasome Pathway - Download this document for free, or read online. Document in PDF available to download.

Studies of brain-specific kinase 2 BRSK2, an AMP-activated protein kinase AMPK-related kinase, and its homologs suggest that they are multifunctional regulators of cell-cycle progression. BRSK2, which contains a ubiquitin-associated UBA domain, is polyubiquitinated in cells. However, the regulatory mechanisms and exact biological function of BRSK2 remain unclear. Herein, we show that BRSK2 co-localizes with the centrosomes during mitosis. We also demonstrate that BRSK2 protein levels fluctuate during the cell cycle, peaking during mitosis and declining in G1 phase. Furthermore, Cdh1, rather than Cdc20, promotes the degradation of BRSK2 in vivo. Consistent with this finding, knock-down of endogenous Cdh1 blocks BRSK2 degradation during the G1 phase. The conserved KEN box of BRSK2 is required for anaphase-promoting complex-cyclosome-Cdh1 APC-CCdh1-dependent degradation. Additionally, overexpression of either BRSK2WT or BRSK2ΔKEN increases the percentage of cells in G2-M. Thus, our results provide the first evidence that BRSK2 regulates cell-cycle progression controlled by APC-CCdh1 through the ubiquitin-proteasome pathway.



Author: Ruwei Li , Bo Wan , Jun Zhou, Yingli Wang, Ting Luo, Xiuting Gu, Fang Chen, Long Yu

Source: http://plos.srce.hr/



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