https://scholars.lib.ntu.edu.tw/handle/123456789/160353
Title: | Interaction between Salt-inducible Kinase 2 (SIK2) and p97/Valosin-containing Protein (VCP) Regulates Endoplasmic Reticulum (ER)-associated Protein Degradation in Mammalian Cells | Authors: | Yang, Fu-Chia Lin, Ya-Huei Chen, Wei-Hao Huang, Jing-Yi Chang, Hsin-Yun Su, Su-Hui Wang, Hsiao-Ting Chiang, Chun-Yi Hsu, Pang-Hung Tsai, Ming-Daw Tan, Bertrand Chin-Ming Lee, Sheng-Chung |
Keywords: | ER Stress;ER-associated Degradation;ERAD;Protein Degradation;Unfolded Protein Response;SIK2;p97;VCP | Issue Date: | 2013 | Start page/Pages: | 33861-33872 | Source: | Journal of Biological Chemistry | Abstract: | Salt-inducible kinase 2 (SIK2) is an important regulator of cAMP response element-binding protein-mediated gene expression in various cell types and is the only AMP-activated protein kinase family member known to interact with the p97/valosin-containing protein (VCP) ATPase. Previously, we have demonstrated that SIK2 can regulate autophagy when proteasomal function is compromised. Here we report that physical and functional interactions between SIK2 and p97/VCP underlie the regulation of endoplasmic reticulum (ER)-associated protein degradation (ERAD). SIK2 co-localizes with p97/VCP in the ER membrane and stimulates its ATPase activity through direct phosphorylation. Although the expression of wild-type recombinant SIK2 accelerated the degradation and removal of ERAD substrates, the kinase-deficient variant conversely had no effect. Furthermore, down-regulation of endogenous SIK2 or mutation of the SIK2 target site on p97/VCP led to impaired degradation of ERAD substrates and disruption of ER homeostasis. Collectively, these findings highlight a mechanism by which the interplay between SIK2 and p97/VCP contributes to the regulation of ERAD in mammalian cells. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/279553 | DOI: | 10.1074/jbc.M113.492199 |
Appears in Collections: | 分子醫學研究所 |
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