A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1.
Phosphorylation of the human p53 protein at Ser-392 has been shown to be responsive to UV but not gamma irradiation. Here we describe identification and purification of a mammalian UV-activated protein kinase complex that phosphorylates Ser-392 of p53 in vitro. This kinase complex contains casein kinase 2 (CK2) and the chromatin transcriptional elongation factor FACT (a heterodimer of hSpt16 and SSRP1). In vitro studies show that FACT alters the specificity of CK2 in the complex such that it selectively phosphorylates p53 over other substrates including casein. In addition, phosphorylation by the kinase complex enhances p53 activity. These results thus provide a potential mechanism for p53 activation by UV irradiation.
Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland, OR 97201, USA.
D M
DM
Keller
X
X
Zeng
Y
Y
Wang
Q H
QH
Zhang
M
M
Kapoor
H
H
Shu
R
R
Goodman
G
G
Lozano
Y
Y
Zhao
H
H
Lu
D000595:Amino Acid Sequence; D047390:Casein Kinase II; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002850:Chromatography, Gel; D017124:Conserved Sequence; D004249:DNA Damage / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation / Q000528:radiation effects; D006609:High Mobility Group Proteins / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D016415:Sequence Alignment; D013379:Substrate Specificity; D014157:Transcription Factors; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays; D054462:p21-Activated Kinases
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D046911:Macromolecular Substances; C073537:SSRP1 protein, human; C489489:SUPT16H protein, human; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D016159:Tumor Suppressor Protein p53; D010768:Phosphoserine; D047390:Casein Kinase II; C515903:PAK1 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases