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Abstract：
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.
摘要：
血清反应因子(SRF),一个关键的转录因子，在调节细胞增殖和分化等功能中起着重要作用。大多数蛋白质不稳定,和蛋白质的稳定性通过泛素-蛋白酶体系统（UPS）或自噬溶酶体途径（ALP）调节。SRF是否降解以及控制SRF蛋白稳定性的机制仍未研究。用环己酰亚胺（CHX）处理的细胞的蛋白质印迹分析，蛋白质合成抑制剂，表明SRF以时间依赖性方式降解。此外，我们观察到SRF经历自噬依赖性破坏，血清剥夺加速了。通过生物信息学筛选,我们发现SRF包含GSK3β磷酸化基序（T/SPPXS）：SPDSPPRSDPT，从斑马鱼到人类都是保守的。血清剥夺刺激GSK3β激活，然后通过自噬溶酶体途径增强SRF降解。由于SRF对许多细胞活动很重要，我们的结果表明,自噬依赖性SRF降解途径可能为调节SRF介导的细胞功能提供了新的途径.
