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Rapid dephosphorylation of p107 following UV irradiation
- Source :
- Oncogene, 18(2), 679. Nature Publishing Group
- Publication Year :
- 1999
-
Abstract
- In response to UV irradiation, mouse NIH3T3 fibroblasts transiently arrest predominantly in the G1 phase of the cell cycle. Here, we investigate the role of the retinoblastoma-related pocket proteins in this biological process. We report here that UV induces an increase in p107/E2F complexes, shown previously to be repressors of E2F-dependent transcriptional activity. Several lines of evidence indicate that the increase of p107/E2F complexes following UV irradiation is a consequence of rapid dephosphorylation of p107. First, UV-mediated p107 dephosphorylation could be abolished by pretreatment of NIH3T3 fibroblasts with the serine/threonine phosphatase inhibitors calyculin A and okadaic acid. Second, alteration of protein phosphatase 2A holoenzyme composition by over-expression of specific B subunits interfered with UV-mediated dephosphorylation of p107. Consistent with this, p107 could be dephosphorylated in vitro with PP2A. Moreover, dephosphorylation of p107 was shown to be independent of the activity of p53 and p21, as it occurred also in UV-treated p53-null as well as p21-null mouse fibroblasts. We observed a close correlation between the UV dosages required for G1 cell cycle arrest and p107 dephosphorylation. Our data suggest a model in which UV radiation-induced cell cycle arrest depends, at least in part, on the induction of a PP2A-like phosphatase that acts on p107.
- Subjects :
- Cyclin-Dependent Kinase Inhibitor p21
Cancer Research
Cell cycle checkpoint
Ultraviolet Rays
Phosphatase
Cell Cycle Proteins
Retinoblastoma-Like Protein p107
Biology
Cell Line
Substrate Specificity
Dephosphorylation
Mice
chemistry.chemical_compound
Cyclins
Okadaic Acid
Phosphoprotein Phosphatases
Tumor Cells, Cultured
Genetics
Animals
Humans
Protein Phosphatase 2
Enzyme Inhibitors
Phosphorylation
Oxazoles
Molecular Biology
G1 Phase
Nuclear Proteins
3T3 Cells
Protein phosphatase 2
Okadaic acid
Cell cycle
E2F Transcription Factors
Cell biology
DNA-Binding Proteins
Enzyme Activation
Biochemistry
chemistry
embryonic structures
Marine Toxins
Tumor Suppressor Protein p53
biological phenomena, cell phenomena, and immunity
Carrier Proteins
Transcription Factor DP1
G1 phase
Biologie
Retinoblastoma-Binding Protein 1
Transcription Factors
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Oncogene, 18(2), 679. Nature Publishing Group
- Accession number :
- edsair.doi.dedup.....ec2890a9ae872e067d85787d8c6f0372