Foxk1 recruits the Sds3 complex and represses gene expression in myogenic progenitors

Xiaozhong Shi, David C. Seldin, Daniel J. Garry

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Previous studies have established that Foxk1 (forkhead box k1) plays an important role in skeletal muscle regeneration. Foxk1 regulates the cell-cycle progression of myogenic progenitors by repressing the cell-cycle inhibitor gene p21. However, the underlying mechanism is not well understood. In the present study, we report the identification of Sds3 (suppressor of defective silencing 3) as an adaptor protein that recruits the Sin3 [SWI (switch)-independent 3]-HDAC (histone deacetylase) repression complex and binds Foxk1. Using GST (glutathione transferase) pull-down assays, we defined the interaction between the Foxk1 FHA (forkhead-associated domain) domain and phospho-Thr49 in Sds3. We demonstrated that the transcriptional repression of Foxk1 is dependent on the Sin3-Sds3 repression complex, and knockdown of Sds3 results in cell-cycle arrest. We further identified the protein kinase CK2 as the protein kinase for Sds3 Thr49 and demonstrated that the protein kinase activity of CK2 is required for proper cell-cycle progression. Analysis of CK2 mutant mice reveals perturbation of skeletal muscle regeneration due to the dysregulation of cell-cycle kinetics. Overall, these studies define a CK2-Sds3-Foxk1 cascade that modulates gene expression and regulates skeletal muscle regeneration.

Original languageEnglish (US)
Pages (from-to)349-357
Number of pages9
JournalBiochemical Journal
Issue number3
StatePublished - Sep 15 2012


  • CK2
  • FHA domain
  • Foxk1
  • Myogenic progenitors
  • Phosphorylation
  • Suppressor of defective silencing 3 (Sds3)


Dive into the research topics of 'Foxk1 recruits the Sds3 complex and represses gene expression in myogenic progenitors'. Together they form a unique fingerprint.

Cite this