title: Phosphorylation of the transcription factor YY1 by CK2α prevents cleavage by caspase 7 during apoptosis.
abstract: In this report, we describe the phosphorylation of Yin Yang 1 (YY1) in vitro and in vivo by CK2α (casein kinase II), a multifunctional serine/threonine protein kinase. YY1 is a ubiquitously expressed multifunctional zinc finger transcription factor implicated in regulation of many cellular and viral genes. The products of these genes are associated with cell growth, the cell cycle, development, and differentiation. Numerous studies have linked YY1 to tumorigenesis and apoptosis. YY1 is a target for cleavage by caspases in vitro and in vivo as well, but very little is known about the mechanisms that regulate its cleavage during apoptosis. Here, we identify serine 118 in the transactivation domain of YY1 as the site of CK2α phosphorylation, proximal to a caspase 7 cleavage site. CK2α inhibitors, as well as knockdown of CK2α by small interfering RNA, reduce S118 phosphorylation in vivo and enhance YY1 cleavage under apoptotic conditions, whereas increased CK2α activity by overexpression in vivo elevates S118 phosphorylation. A serine-to-alanine substitution at serine 118 also increases the cleavage of YY1 during apoptosis compared to wild-type YY1. Taken together, we have discovered a regulatory link between YY1 phosphorylation at serine 118 and regulation of its cleavage during programmed cell death.
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Riman
authors.forename: Raed
authors.initials: R
authors.lastname: Rizkallah
authors.forename: Ari
authors.initials: A
authors.lastname: Kassardjian
authors.forename: Karen E
authors.initials: KE
authors.lastname: Alexander
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lüscher
authors.forename: Myra M
authors.initials: MM
authors.lastname: Hurt
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D001665:Binding Sites; D047390:Casein Kinase II / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D050986:YY1 Transcription Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D011994:Recombinant Proteins; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D012694:Serine; C570325:CSNK2A1 protein, human; D047390:Casein Kinase II; C505520:CASP7 protein, human; D053179:Caspase 7