1. Academic Validation
  2. c-Abl phosphorylation of Yin Yang 1's conserved tyrosine 254 in the spacer region modulates its transcriptional activity

c-Abl phosphorylation of Yin Yang 1's conserved tyrosine 254 in the spacer region modulates its transcriptional activity

  • Biochim Biophys Acta Mol Cell Res. 2018 Sep;1865(9):1173-1186. doi: 10.1016/j.bbamcr.2018.05.014.
Susan I Daraiseh 1 Ari Kassardjian 2 Karen E Alexander 1 Raed Rizkallah 1 Myra M Hurt 3
Affiliations

Affiliations

  • 1 Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, USA.
  • 2 David Geffen School of Medicine, Department of Pathology and Laboratory Medicine at UCLA, Los Angeles, CA, USA.
  • 3 Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, USA. Electronic address: myra.hurt@med.fsu.edu.
Abstract

Yin Yang 1 (YY1) is a multifunctional transcription factor that can activate or repress transcription depending on the promotor and/or the co-factors recruited. YY1 is phosphorylated in various signaling pathways and is critical for different biological functions including embryogenesis, Apoptosis, proliferation, cell-cycle regulation and tumorigenesis. Here we report that YY1 is a substrate for c-Abl kinase phosphorylation at conserved residue Y254 in the spacer region. Pharmacological inhibition of c-Abl kinase by imatinib, nilotinib and GZD824, knock-down of c-Abl using siRNA, and the use of c-Abl kinase-dead drastically reduces tyrosine phosphorylation of YY1. Both radioactive and non-radioactive in vitro kinase assays, as well as co-immunoprecipitation in different cell lines, show that the target of c-Abl phosphorylation is tyrosine residue 254. c-Abl phosphorylation has little effect on YY1 DNA binding ability or cellular localization in asynchronous cells. However, functional studies reveal that c-Abl mediated phosphorylation of YY1 regulates YY1's transcriptional ability in vivo. In conclusion, we demonstrate the novel role of c-Abl kinase in regulation of YY1's transcriptional activity, linking YY1 regulation with c-Abl tyrosine kinase signaling pathways.

Keywords

Gene regulation; Protein phosphorylation; Transcription factor; Tyrosine kinase; YY1; c-Abl.

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