Regulation of SRF protein stability by an autophagy-dependent pathway.
Regulation of SRF protein stability by an autophagy-dependent pathway.
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DOI：
10.1016/j.bbrc.2019.09.104
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发表时间：
2020-01
影响因子：
3.1
通讯作者：
Jinque Luo;F. Q. Jin;Meimei Yin;Z. Jin
中科院分区：
文献类型：
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作者：
Jinque Luo;F. Q. Jin;Meimei Yin;Z. Jin
血清反应因子（serum response factor，SRF）是一种重要的转录因子，在调节细胞增殖和分化等功能中发挥重要作用。大多数蛋白质是不稳定的，并且蛋白质稳定性通过泛素-蛋白酶体系统（UPS）或自噬溶酶体途径（ALP）来调节。SRF是否被降解，以及控制SRF蛋白稳定性的机制仍有待研究。蛋白质合成抑制剂放线菌酮（CHX）处理的细胞的蛋白质印迹分析表明，SRF降解的时间依赖性的方式。此外，我们观察到SRF经历自噬依赖性破坏，这是由血清剥夺加速。通过生物信息学筛选，我们发现SRF中含有GSK 3 β磷酸化基序（T/SPPXS）：SPDSPPRSDPT，该基序在斑马鱼和人类中都是保守的。血清剥夺刺激GSK 3 β活化，然后通过自噬溶酶体途径加强SRF降解。由于SRF对许多细胞活动都很重要，我们的研究结果表明，自噬依赖的SRF降解途径可能提供一个新的途径来调节SRF介导的细胞功能。
Serum response factor (SRF), a key transcription factor, plays an important role in regulating cell functions such as proliferation and differentiation. Most proteins are unstable, and protein stability is regulated through the ubiquitin-proteasome system (UPS) or the autophagy lysosome pathway (ALP). Whether SRF is degraded and what mechanisms control SRF protein stability remain unexplored. Western blot analyses of cells treated with cycloheximide (CHX), a protein synthesis inhibitor, showed that SRF was degraded in a time-dependent manner. Moreover, we observed that SRF undergoes autophagy-dependent destruction, which is accelerated by serum deprivation. Through bioinformatics screening, we found that SRF contains the GSK3β phosphorylation motif (T/SPPXS): SPDSPPRSDPT, which is conserved from zebrafish to humans. Serum deprivation stimulated GSK3β activation that then potentiates SRF degradation through the autophagy lysosome pathway. Since SRF is important for numerous cellular activities, our results suggest that the autophagy-dependent SRF degradation pathway may provide a new avenue to modulate SRF-mediated cell functions.