Alternatively spliced forms in the carboxy-terminal domain of the p53 protein regulate its ability to promote annealing of complementary single strands of nucleic acids

The carboxy-terminal domain of the p53 protein comprising amino acid residues 311 to 393 is able to promote the reassociation of single-stranded RNA or DNA into duplex hybrids. This domain is as efficient as the intact p53 protein in both the rate and the extent of the double-stranded product produced in this reaction. Both wild-type and mutant p53 proteins from cancerous cells carry out this reaction. The monoclonal antibody PAb421, which detects an epitope between residues 370 and 378, blocks the ability of p53 to reassociate single strands of RNA or DNA. Similarly, the alternative splice form of the murine p53 protein, which removes amino acid residues 364 to 390 and replaces them with 17 new amino acids, does not carry out the reassociation reaction with RNA or DNA. This is the first indication of functionally distinct properties of the alternative splice forms of p53. These results suggest that this splice alternative can regulate a p53-mediated reaction that may be related to the functions of this protein.

[1]  A. Levine,et al.  Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. , 1994, Genes & development.

[2]  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.

[3]  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.

[4]  L. Szekely,et al.  p53 binds single-stranded DNA ends and catalyzes DNA renaturation and strand transfer. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[5]  J. E. Stenger,et al.  p53 domains: identification and characterization of two autonomous DNA-binding regions. , 1993, Genes & development.

[6]  X. Chen,et al.  A proteolytic fragment from the central region of p53 has marked sequence-specific DNA-binding activity when generated from wild-type but not from oncogenic mutant p53 protein. , 1993, Genes & development.

[7]  C. Pabo,et al.  The DNA-binding domain of p53 contains the four conserved regions and the major mutation hot spots. , 1993, Genes & development.

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

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

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

[11]  Scott W. Lowe,et al.  p53 is required for radiation-induced apoptosis in mouse thymocytes , 1993, Nature.

[12]  C. Purdie,et al.  Thymocyte apoptosis induced by p53-dependent and independent pathways , 1993, Nature.

[13]  G. Zambetti,et al.  Wild-type p53 binds to the TATA-binding protein and represses transcription. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[14]  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.

[15]  Thea D. Tlsty,et al.  Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53 , 1992, Cell.

[16]  G. Wahl,et al.  Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles , 1992, Cell.

[17]  M. Remm,et al.  A C-terminal alpha-helix plus basic region motif is the major structural determinant of p53 tetramerization. , 1992, Oncogene.

[18]  A. Levine,et al.  Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[19]  P. Friedman,et al.  Wild-type p53 activates transcription in vitro , 1992, Nature.

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

[21]  P. Shaw,et al.  Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[22]  M. Kulesz-Martin,et al.  Alternatively spliced p53 RNA in transformed and normal cells of different tissue types. , 1992, Nucleic acids research.

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

[24]  V. Rotter,et al.  Involvement of wild-type p53 protein in the cell cycle requires nuclear localization. , 1991, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[25]  M. Yaniv,et al.  Wild-type p53 can down-modulate the activity of various promoters. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[26]  A. Kimchi,et al.  Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6 , 1991, Nature.

[27]  B. Vogelstein,et al.  Wild-type but not mutant p53 immunopurified proteins bind to sequences adjacent to the SV40 origin of replication , 1991, Cell.

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

[29]  G. Lozano,et al.  Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene. , 1990, Science.

[30]  S. Fields,et al.  Presence of a potent transcription activating sequence in the p53 protein. , 1990, Science.

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

[32]  P. Friedman,et al.  Human p53 is phosphorylated by p60-cdc2 and cyclin B-cdc2. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[33]  T. Maimets,et al.  p53 interacts with p34cdc2 in mammalian cells: implications for cell cycle control and oncogenesis. , 1990, Oncogene.

[34]  A. Levine,et al.  Purification of complexes of nuclear oncogene p53 with rat and Escherichia coli heat shock proteins: in vitro dissociation of hsc70 and dnaK from murine p53 by ATP , 1988, Molecular and cellular biology.

[35]  L. Banks,et al.  Isolation of human-p53-specific monoclonal antibodies and their use in the studies of human p53 expression. , 1986, European journal of biochemistry.

[36]  J. Yewdell,et al.  Monoclonal antibody analysis of p53 expression in normal and transformed cells , 1986, Journal of virology.

[37]  V. Rotter,et al.  Isolation of a full-length mouse cDNA clone coding for an immunologically distinct p53 molecule , 1985, Molecular and cellular biology.

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

[39]  D. Pim,et al.  Monoclonal antibodies specific for simian virus 40 tumor antigens , 1981, Journal of virology.

[40]  K. Kinzler,et al.  Oncogenic forms of p53 inhibit p53-regulated gene expression. , 1992, Science.

[41]  J. Milner,et al.  A new anti-p53 monoclonal antibody, previously reported to be directed against the large T antigen of simian virus 40. , 1987, Oncogene.