https://scholars.lib.ntu.edu.tw/handle/123456789/160352
標題: | Reversible Acetylation Regulates Salt-inducible Kinase (SIK2) and Its Function in Autophagy | 作者: | Yang, Fu-Chia Tan, Bertrand Chin-Ming Chen, Wei-Hao Lin, Ya-Huei Huang, Jing-Yi Chang, Hsin-Yun Sun, Hui-Yu Hsu, Pang-Hung Liou, Gunn-Guang Shen, James Chang, Ching-Jin Han, Chau-Chung Tsai, Ming-Daw Lee, Sheng-Chung |
公開日期: | 2013 | 起(迄)頁: | 6227-6237 | 來源出版物: | Journal of Biological Chemistry | 摘要: | Salt-inducible kinase 2 (SIK2) is a serine/threonine protein kinase belonging to the AMP-activated protein kinase (AMPK) family. SIK2 has been shown to function in the insulin-signaling pathway during adipocyte differentiation and to modulate CREB-mediated gene expression in response to hormones and nutrients. However, molecular mechanisms underlying the regulation of SIK2 kinase activity remains largely elusive. Here we report a dynamic, post-translational regulation of its kinase activity that is coordinated by an acetylation-deaceytlation switch, p300/CBP-mediated Lys-53 acetylation inhibits SIK2 kinase activity, whereas HDAC6-mediated deacetylation restores the activity. Interestingly, overexpression of acetylation-mimetic mutant of SIK2 (SIK2-K53Q), but not the nonacetylatable K53R variant, resulted in accumulation of autophagosomes. Further consistent with a role in autophagy, knockdown of SIK2 abrogated autophagosome and lysosome fusion. Consequently, SIK2 and its kinase activity are indispensable for the removal of TDP-43 Delta inclusion bodies. Our findings uncover SIK2 as a critical determinant in autophagy progression and further suggest a mechanism in which the interplay among kinase and deacetylase activities contributes to cellular protein pool homeostasis. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/279524 | DOI: | 10.1074/jbc.M112.431239 |
顯示於: | 分子醫學研究所 |
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