Tumour suppressors, kinases and clamps: How p53 regulates the cell cycle in response to DNA damage

The human tumour suppressor protein p53 is critical for regulation of the cell cycle on genotoxic insult. When DNA is damaged by radiation, chemicals or viral infection, cells respond rapidly by arresting the cell cycle. A G1 arrest requires the activity of wild‐type p53, as it is not observed in cells lacking functionally wild‐type protein, and at least some component of S phase and G2/M arrests is also thought to be p53‐dependent. p53 functions as a transcription factor which binds specific DNA sequences, and recently major downstream targets have been identified, including p21Cip1 an inhibitor of the cell cycle kinases that also blocks the replicative but not the repair function of DNA polymerase δ auxiliary factor, PCNA. Current interest focuses on developing novel cancer therapies based on our knowledge of the activity of p53 and p21Cip1 in the cell cycle.

[1]  D. Lane,et al.  p53-dependent growth arrest following calcium phosphate-mediated transfection of murine fibroblasts. , 1995, Oncogene.

[2]  L. Cox,et al.  A direct effect of activated human p53 on nuclear DNA replication. , 1995, The EMBO journal.

[3]  D. Lane,et al.  A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor p21WAF1 and proliferating cell nuclear antigen , 1995, Current Biology.

[4]  J. R. Smith,et al.  Identification of the active region of the DNA synthesis inhibitory gene p21Sdi1/CIP1/WAF1. , 1995, The EMBO journal.

[5]  R. Tjian,et al.  p53 transcriptional activation mediated by coactivators TAFII40 and TAFII60. , 1995, Science.

[6]  G. Hicks,et al.  Evidence for a second cell cycle block at G2/M by p53. , 1995, Oncogene.

[7]  J. Little,et al.  Radiation-induced irreversible g(0) g(1) block is abolished in human-diploid fibroblasts transfected with the human papilloma-virus e6 gene - implication of the p53-cip1 waf1 pathway. , 1995, International journal of oncology.

[8]  K. Vousden,et al.  Transcriptional activation by p53 correlates with suppression of growth but not transformation , 1994, Cell.

[9]  M. Sheikh,et al.  Mechanisms of regulation of WAF1/Cip1 gene expression in human breast carcinoma: role of p53-dependent and independent signal transduction pathways. , 1994, Oncogene.

[10]  U. Strausfeld,et al.  Cip1 inhibits DNA replication but not PCNA-dependent nucleotide excision—repair , 1994, Current Biology.

[11]  P. O'Connor,et al.  Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. , 1994, Science.

[12]  M. Fiscella,et al.  The carboxy-terminal serine 392 phosphorylation site of human p53 is not required for wild-type activities. , 1994, Oncogene.

[13]  G. Hannon,et al.  Differential effects by the p21 CDK inhibitor on PCNA-dependent DNA replication and repair , 1994, Nature.

[14]  D. Lane,et al.  Xenopus p53 is biochemically similar to the human tumour suppressor protein p53 and is induced upon DNA damage in somatic cells. , 1994, Oncogene.

[15]  D. Beach,et al.  Cyclin G is a transcriptional target of the p53 tumor suppressor protein. , 1994, The EMBO journal.

[16]  S. Reed,et al.  Molecular cloning, sequencing, chromosomal localization and expression of mouse p21 (Waf1). , 1994, Oncogene.

[17]  K. Ogawa,et al.  Indistinct cell cycle checkpoint after u.v. damage in H-ras-transformed mouse liver cells despite normal p53 gene expression. , 1994, Oncogene.

[18]  D. Lane,et al.  Immunochemical analysis of the interaction of p53 with MDM2;--fine mapping of the MDM2 binding site on p53 using synthetic peptides. , 1994, Oncogene.

[19]  J. Rayner,et al.  Transcriptional regulation of the PCNA promoter by p53. , 1994, Biochemical and biophysical research communications.

[20]  S. Lowe,et al.  p53-Dependent apoptosis suppresses tumor growth and progression in vivo , 1994, Cell.

[21]  K. Vousden,et al.  Cells expressing HPV16 E7 continue cell cycle progression following DNA damage induced p53 activation. , 1994, Oncogene.

[22]  G. Hannon,et al.  p21-containing cyclin kinases exist in both active and inactive states. , 1994, Genes & development.

[23]  M. Karin,et al.  p53-Dependent apoptosis in the absence of transcriptional activation of p53-target genes , 1994, Nature.

[24]  P. Jeffrey,et al.  Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. , 1994, Science.

[25]  K. Matsubara,et al.  Identification of cellular proteins that bind the central conserved region of p53. , 1994, Biochemical and biophysical research communications.

[26]  R. Brown,et al.  Cell cycle arrests and radiosensitivity of human tumor cell lines: dependence on wild-type p53 for radiosensitivity. , 1994, Cancer research.

[27]  S. Fields,et al.  Two cellular proteins that bind to wild-type but not mutant p53. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[28]  M. Clarke,et al.  c-myc and bcl-2 modulate p53 function by altering p53 subcellular trafficking during the cell cycle. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[29]  G. Hannon,et al.  The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA , 1994, Nature.

[30]  Kathleen R. Cho,et al.  p53-dependent G1 arrest involves pRB-related proteins and is disrupted by the human papillomavirus 16 E7 oncoprotein. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[31]  J. Pelling,et al.  Increase in p53 protein half-life in mouse keratinocytes following UV-B irradiation. , 1994, Carcinogenesis.

[32]  John Calvin Reed,et al.  Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. , 1994, Oncogene.

[33]  J. Jenkins,et al.  Human p53 directs DNA strand reassociation and is photolabelled by 8-azido ATP. , 1994, Oncogene.

[34]  John Calvin Reed,et al.  Immediate early up-regulation of bax expression by p53 but not TGF beta 1: a paradigm for distinct apoptotic pathways. , 1994, Oncogene.

[35]  A. Fornace,et al.  The p53-dependent γ-Ray Response of GADD45 , 1994 .

[36]  G. Demers,et al.  Growth arrest by induction of p53 in DNA damaged keratinocytes is bypassed by human papillomavirus 16 E7. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[37]  R. Chinery,et al.  p53 expression in cultured cells following radioisotope labelling. , 1994, Journal of cell science.

[38]  A. Levine,et al.  p53 and E2F-1 cooperate to mediate apoptosis. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[39]  K. Khanna,et al.  Ionizing radiation and cell cycle progression in ataxia telangiectasia. , 1994, Radiation research.

[40]  B. Vogelstein,et al.  Interactions between p53 and MDM2 in a mammalian cell cycle checkpoint pathway. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[41]  Stephen J. Elledge,et al.  p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest , 1994, Cell.

[42]  K. Kinzler,et al.  Sequence-specific transcriptional activation is essential for growth suppression by p53. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[43]  C. Harris,et al.  Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[44]  J. R. Smith,et al.  Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. , 1994, Experimental cell research.

[45]  F. Diella,et al.  Expression of wild-type p53 during the cell cycle in normal human mammary epithelial cells. , 1994, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[46]  M. Kulesz-Martin,et al.  Endogenous p53 protein generated from wild-type alternatively spliced p53 RNA in mouse epidermal cells , 1994, Molecular and cellular biology.

[47]  M. Kastan,et al.  DNA strand breaks: the DNA template alterations that trigger p53-dependent DNA damage response pathways , 1994, Molecular and cellular biology.

[48]  M. Montenarh,et al.  Overexpression of wild-type p53 interferes with normal development in Xenopus laevis embryos. , 1994, Oncogene.

[49]  C. Turck,et al.  Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit , 1993, Nature.

[50]  David Beach,et al.  p21 is a universal inhibitor of cyclin kinases , 1993, Nature.

[51]  A. Levine,et al.  The mdm-2 gene is induced in response to UV light in a p53-dependent manner. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[52]  M. Oren,et al.  Wild type p53 can mediate sequence-specific transactivation of an internal promoter within the mdm2 gene. , 1993, Oncogene.

[53]  K. Khanna,et al.  Ionizing radiation and UV induction of p53 protein by different pathways in ataxia-telangiectasia cells. , 1993, Oncogene.

[54]  Xin Lu,et al.  Differential induction of transcriptionally active p53 following UV or lonizing radiation: Defects in chromosome instability syndromes? , 1993, Cell.

[55]  J. Trent,et al.  WAF1, a potential mediator of p53 tumor suppression , 1993, Cell.

[56]  S. Elledge,et al.  The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases , 1993, Cell.

[57]  X. Chen,et al.  Cooperative DNA binding of p53 with TFIID (TBP): a possible mechanism for transcriptional activation. , 1993, Genes & development.

[58]  E. Winchester,et al.  Inhibition of DNA replication factor RPA by p53 , 1993, Nature.

[59]  T. Soussi,et al.  Stabilization and expression of high levels of p53 during early development in Xenopus laevis. , 1993, Developmental biology.

[60]  D. Lane,et al.  Activation of the cryptic DNA binding function of mutant forms of p53. , 1993, Nucleic acids research.

[61]  J. M. Lee,et al.  p53 mutations increase resistance to ionizing radiation. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[62]  U. Ramsperger,et al.  p53‐catalyzed annealing of complementary single‐stranded nucleic acids. , 1993, The EMBO journal.

[63]  M. Fiscella,et al.  Mutation of the serine 15 phosphorylation site of human p53 reduces the ability of p53 to inhibit cell cycle progression. , 1993, Oncogene.

[64]  M. Oren,et al.  mdm2 expression is induced by wild type p53 activity. , 1993, The EMBO journal.

[65]  D. Lane,et al.  High levels of p53 protein in UV-irradiated normal human skin. , 1993, Oncogene.

[66]  P. Howley,et al.  The transcriptional transactivation function of wild‐type p53 is inhibited by SV40 large T‐antigen and by HPV‐16 E6 oncoprotein. , 1992, The EMBO journal.

[67]  E. Shaulian,et al.  Identification of a minimal transforming domain of p53: negative dominance through abrogation of sequence-specific DNA binding , 1992, Molecular and cellular biology.

[68]  B. Vogelstein,et al.  A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia , 1992, Cell.

[69]  D. Meek,et al.  Mutation of the casein kinase II phosphorylation site abolishes the anti-proliferative activity of p53. , 1992, Nucleic acids research.

[70]  Hui Zhang,et al.  D type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA , 1992, Cell.

[71]  D. Meek,et al.  Nuclear protein phosphorylation and growth control. , 1992, The Biochemical journal.

[72]  B. Seizinger,et al.  Repression of the basal c-fos promoter by wild-type p53. , 1992, Nucleic acids research.

[73]  E. Appella,et al.  Human wild-type p53 adopts a unique conformational and phosphorylation state in vivo during growth arrest of glioblastoma cells. , 1992, Oncogene.

[74]  M. Subler,et al.  Inhibition of viral and cellular promoters by human wild-type p53 , 1992, Journal of virology.

[75]  D. Lane,et al.  ras-Induced hyperplasia occurs with mutation of p53, but activated ras and myc together can induce carcinoma without p53 mutation , 1992, Cell.

[76]  D. Lane,et al.  p53, guardian of the genome , 1992, Nature.

[77]  A. Levine,et al.  The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation , 1992, Cell.

[78]  K. Kinzler,et al.  Definition of a consensus binding site for p53 , 1992, Nature Genetics.

[79]  L. Donehower,et al.  Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours , 1992, Nature.

[80]  J. Sherley.  Guanine nucleotide biosynthesis is regulated by the cellular p53 concentration. , 1991, The Journal of biological chemistry.

[81]  B. Vogelstein,et al.  Participation of p53 protein in the cellular response to DNA damage. , 1991, Cancer research.

[82]  V. Rotter,et al.  Nuclear localization is essential for the activity of p53 protein. , 1991, Oncogene.

[83]  B. Vogelstein,et al.  p53 mutations in human cancers. , 1991, Science.

[84]  David P. Lane,et al.  Protein synthesis required to anchor a mutant p53 protein which is temperature-sensitive for nuclear transport , 1991, Nature.

[85]  A. Levine,et al.  Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein. , 1991, Genes & development.

[86]  D. Lane,et al.  Localization of p53, retinoblastoma and host replication proteins at sites of viral replication in herpes-infected cells , 1991, Nature.

[87]  C. Anderson,et al.  Human cells contain a DNA-activated protein kinase that phosphorylates simian virus 40 T antigen, mouse p53, and the human Ku autoantigen , 1990, Molecular and cellular biology.

[88]  V. Rotter,et al.  Subcellular distribution of the p53 protein during the cell cycle of Balb/c 3T3 cells. , 1990, Oncogene.

[89]  T. Curran,et al.  Redox regulation of fos and jun DNA-binding activity in vitro. , 1990, Science.

[90]  O. Halevy,et al.  Conditional inhibition of transformation and of cell proliferation by a temperature-sensitive mutant of p53 , 1990, Cell.

[91]  T. Soussi,et al.  Structural aspects of the p53 protein in relation to gene evolution. , 1990, Oncogene.

[92]  E. Appella,et al.  Wild type human p53 is antiproliferative in SV40-transformed hamster cells. , 1990, Oncogene.

[93]  J. Jenkins,et al.  The p53 nuclear localisation signal is structurally linked to a p34cdc2 kinase motif. , 1990, Oncogene.

[94]  W. Maltzman,et al.  UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells , 1984, Molecular and cellular biology.

[95]  A. Levine,et al.  Growth regulation of a cellular tumour antigen, p53, in nontransformed cells , 1984, Nature.