國家衛生研究院 NHRI:Item 3990099045/7112
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    题名: Reversible acetylation regulates salt-inducible kinase (SIK2) and its function in autophagy
    作者: Yang, FC;Tan, BCM;Chen, WH;Lin, YH;Huang, JY;Chang, HY;Sun, HY;Hsu, PH;Liou, GG;Shen, J;Chang, CJ;Han, CC;Tsai, MD;Lee, SC
    贡献者: Institute of Molecular and Genomic Medicine
    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-43Δ 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.
    日期: 2013-03-01
    關聯: Journal of Biological Chemistry. 2013 Mar 1;288(9):6227-6237.
    Link to: http://dx.doi.org/10.1074/jbc.M112.431239
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1083-351X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000315820700018
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84874769490
    显示于类别:[劉淦光(2006-2014)] 期刊論文

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