apcccdh1 targets brain-specific kinase 2 (brsk2) for degradation via the ubiquitin-proteasome pathwayapcccdh1目标brain-specific激酶2(brsk2)通过ubiquitin-proteasome降解途径.pdfVIP

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apcccdh1 targets brain-specific kinase 2 (brsk2) for degradation via the ubiquitin-proteasome pathwayapcccdh1目标brain-specific激酶2(brsk2)通过ubiquitin-proteasome降解途径.pdf

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apcccdh1 targets brain-specific kinase 2 (brsk2) for degradation via the ubiquitin-proteasome pathwayapcccdh1目标brain-specific激酶2(brsk2)通过ubiquitin-proteasome降解途径

APC/CCdh1 Targets Brain-Specific Kinase 2 (BRSK2) for Degradation via the Ubiquitin-Proteasome Pathway . . Ruwei Li , Bo Wan , Jun Zhou, Yingli Wang, Ting Luo, Xiuting Gu, Fang Chen, Long Yu* State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People’s Republic of China Abstract 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 BRSK2(WT) or BRSK2(DKEN) 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. Citation: Li R, Wan B, Zhou J, Wang Y, Luo T, et al. (2012) APC/CCdh1 Targets Brain-Specific Kinase 2 (BRSK2) for Degradation via the Ubiquitin-Proteasome Pathway. PLoS ONE 7(9): e45932. doi:10.1371/journal.pone.0045932 Editor: Deanna M. Koepp, University of Minnesota, United States of America Rec