title: Regulation of Yin Yang 1 by Tyrosine Phosphorylation.
abstract: Yin Yang 1 (YY1) is a member of the GLI-Krüppel class of DNA and RNA binding transcription factors that can either activate or repress gene expression during cell growth, differentiation, and embryogenesis. Although much is known about YY1 interacting proteins and the target promoters regulated by YY1, much less is known about YY1 regulation through post-translational modifications. In this study we show that YY1 is tyrosine-phosphorylated in multiple cell types. Using a combination of pharmacological inhibition, kinase overexpression, and kinase knock-out studies, we demonstrate that YY1 is a target of multiple Src family kinases in vitro and in vivo. Moreover, we have identified multiple sites of YY1 phosphorylation and analyzed the effect of phosphorylation on the activity of YY1-responsive retroviral and cellular promoters. Phosphorylation of tyrosine 383 interferes with DNA and RNA binding, leading to the down-regulation of YY1 activity. Finally, we provide the first evidence that YY1 is a downstream target of epidermal growth factor receptor signaling in vivo. Taken together, the identification of YY1 as a target of Src family kinases provide key insights into the inhibitory role of tyrosine kinases in modulating YY1 activity.
authors.affiliation: From the Integrated Program in Cellular, Molecular, and Biophysical Studies, Medical Scientist Training Program, Columbia University College of Physicians and Surgeons, New York, New York 10032.
authors.forename: Gary Z
authors.initials: GZ
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Department of Microbiology and Immunology, and Howard Hughes Medical Institute, Columbia University, New York, New York 10032 and spg1@columbia.edu.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Goff
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D019169:Jurkat Cells; D009154:Mutation; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D016760:Proto-Oncogene Proteins c-fos; C416927:SU 6656; D013449:Sulfonamides; D050986:YY1 Transcription Factor; D014443:Tyrosine; D004815:Epidermal Growth Factor; D000068877:Imatinib Mesylate; D019061:src-Family Kinases
keywords: Src; gene regulation; phosphotyrosine; protein phosphorylation; retrovirus; transcription factor