Protein phosphatase 1, but not protein phosphatase 2A, dephosphorylates DNA-damaging stress-induced phospho-serine 15 of p53.
Okadaic acid (OA) is a protein phosphatase (PP) inhibitor and induces hyperphosphorylation of p53. We investigated whether the inhibition of PP1 by OA promotes the phosphorylation of the serine 15 of p53. In vitro dephosphorylation assay showed that PP1 dephosphorylated ultraviolet C (UVC)-induced phospho-ser15 of p53, and that OA treatment inhibited it. One of the PP1 regulators, growth arrest and DNA damage 34 (GADD34), disturbed PP1 binding with p53, interfered with the dephosphorylation of p53 and increased the amount of phospho-p53 after UVC-treatment. This report provides the first evidence that PP1, but not PP2A, dephosphorylates phospho-serine 15 of p53.
Haneda
Masataka
M
Department of Basic Gerontology, National Institute for Longevity Sciences, 36-3 Gengo, Morioka-cho, Obu, Aichi 474-8522, Japan.
Kojima
Eiji
E
Nishikimi
Akihiko
A
Hasegawa
Tadao
T
Nakashima
Izumi
I
Isobe
Ken-ichi
K
D000818:Animals; D000943:Antigens, Differentiation; D000952:Antigens, Polyomavirus Transforming / Q000494:pharmacology; D018797:Cell Cycle Proteins; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology* / Q000528:radiation effects; D004622:Embryo, Mammalian / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
D000943:Antigens, Differentiation; D000952:Antigens, Polyomavirus Transforming; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D015852:Eukaryotic Initiation Factor-2; D011506:Proteins; D016159:Tumor Suppressor Protein p53; D010768:Phosphoserine; D019319:Okadaic Acid; D008741:Methyl Methanesulfonate; C087519:PPP1R15A protein, human; D010749:Phosphoprotein Phosphatases; C513256:Ppp1r15a protein, mouse; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2