1. Regulation of SRF protein stability by an autophagy-dependent pathway
- Author
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Meimei Yin, Felix Q Jin, Zheng Gen Jin, and Jinque Luo
- Subjects
0301 basic medicine ,Serum Response Factor ,genetic structures ,Biophysics ,Cycloheximide ,Biochemistry ,Article ,Culture Media, Serum-Free ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Western blot ,Lysosome ,Serum response factor ,Chlorocebus aethiops ,medicine ,Autophagy ,Animals ,Humans ,Molecular Biology ,Zebrafish ,Gene ,Transcription factor ,Cells, Cultured ,Glycogen Synthase Kinase 3 beta ,biology ,medicine.diagnostic_test ,Chemistry ,Protein Stability ,Cell Biology ,biology.organism_classification ,musculoskeletal system ,eye diseases ,Cell biology ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,embryonic structures ,COS Cells ,cardiovascular system ,Lysosomes - 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.
- Published
- 2019