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Mdm-2 binding and TAFII31 recruitment is regulated by hydrogen bond disruption between the p53 residues Thr18 and Asp21

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Abstract

Analyses of five wild-type p53 containing cell lines revealed lineage specific differences in phosphorylation of Thr18 after treatment with ionizing (IR) or ultraviolet (UV) radiation. Importantly, Thr18 phosphorylation correlated with induction of the p53 downstream targets p21Waf1/Cip1 (p21) and Mdm-2, suggesting a transactivation enhancing role. Thr18 phosphorylation has been shown to abolish side-chain hydrogen bonding between Thr18 and Asp21, an interaction necessary for stabilizing alpha–helical conformation within the transactivation domain. Mutagenesis-derived hydrogen bond disruption attenuated the interaction of p53 with the transactivation repressor Mdm-2 but had no direct effect on the interaction of p53 with the basal transcription factor TAFII31. However, prior incubation of p53 mutants with Mdm-2 modulated TAFII31 interaction with p53, suggesting Mdm-2 blocks the accessibility of p53 to TAFII31. Consistently, p53-null cells transfected with hydrogen bond disrupting p53 mutants demonstrated enhanced endogenous p21 expression, whereas p53/Mdm-2-double null cells exhibited no discernible differences in p21 expression. We conclude disruption of intramolecular hydrogen bonding between Thr18 and Asp21 enhances p53 transactivation by modulating Mdm-2 binding, facilitating TAFII31 recruitment.

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References

  • Avantaggiati ML, Ogryzko V, Gardner K, Giordano A, Levine AS, Kelly K . 1997 Cell 89: 1175–1184

  • Banin S, Moyal L, Khostravi R, Shieh SY, Taya Y, Anderson CW, Chessa L, Smorodinsky NI, Prives C, Shiloh Y, Ziv Y . 1998 Science 281: 1674–1677

  • Bottger V, Bottger A, Garcia-Echeverria C, Ramos YF, van der Eb AJ, Jochemsen AG, Lane DP . 1999 Oncogene 18: 189–199

  • Bulavin DV, Saito S, Hollander MC, Sakaguchi K, Anderson CW, Appella E, Fornace AJ . 1999 EMBO J. 18: 6845–6854

  • Canagarajah BJ, Khokhlatchev A, Cobb MH, Goldsmith EJ . 1997 Cell 90: 859–869

  • Canman DE, Lim DS, Cimprich KA, Taya Y, Tamai K, Sakaguchi K, Appella E, Kastan MB, Siliciano DD . 1998 Science 281: 1677–1679

  • Chehab NH, Malikzay A, Appel M, Halazonetis TD . 2000 Genes Dev. 14: 278–288

  • Chehab NH, Malikzay A, Stavridi ES, Halazonetis TD . 1999 Proc. Natl. Acad. Sci. USA 96: 13777–13782

  • Chen X, Farmer G, Zhu H, Prywes R, Prives C . 1993 Genes Dev. 7: 1837–1849

  • Choi Y, Asada S, Uesugi M . 2000 J. Biol. Chem. 275: 15912–15916

  • Collins A . 1987 Int. J. Radia. Biol. Relat. Stud. Phys. Chem. Med. 51: 971–983

  • Craig AL, Burch L, Vojtesek B, Mikutowska J, Thompson A, Hupp TR . 1999 British J. Biochem. 342: 133–141

  • Drouin R, Therrien JP . 1997 Photochem. Photobiol. 66: 719–726

  • Dumaz N, Meek DW . 1999 EMBO J. 24: 7002–7010

  • Dumaz N, Milne DM, Meek DW . 1999 FEBS Lett. 463: 312–316

  • de Oca Luna RM, Wagner DS, Lozano G . 1995 Nature 378: 203–206

  • El-Deiry WS . 1998 Semin. Cancer Biol. 8: 345–357

  • Farmer G, Colgan J, Nakatani Y, Manley JL, Prives C . 1996 Mol. Cell. Biol. 16: 4295–4303

  • Feng S, Jensen JP, Ludwig RL, Vousden KH, Weissman AM . 2000 J. Biol. Chem. 275: 8945–8951

  • Giaccia AJ, Kastan MB . 1998 Genes Dev. 12: 2973–2983

  • Grossman SR, Perez M, Kung AL, Joseph M, Mansur C, ** Zhang for their helpful assistance and discussion. This work was supported in part by NIH grant CA67987. JR Jabbur was a recipient of the American Legion Auxiliary Fellowship.

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Authors and Affiliations

  1. Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, Texas, TX, USA

    James R Jabbur, Amy D Tabor, Hua Wang & Wei Zhang

  2. Department of Molecular Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, Texas, TX, USA

    Hua Wang & Guillermina Lozano

  3. Cancer Genomics Laboratory, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, Texas, TX, USA

    James R Jabbur, Amy D Tabor, Hua Wang & Wei Zhang

  4. Graduate Program in Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, Texas, TX, USA

    James R Jabbur, Guillermina Lozano & Wei Zhang

  5. Graduate Program in Genes and Development, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, Texas, TX, USA

    Hua Wang

  6. Sealy Center for Structural Biology and the Department of Pharmacology and Toxicology, The University of Texas Medical Branch at Galveston, Galveston, 77555, Texas, TX, USA

    **aodong Cheng

  7. Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, 77030, Texas, TX, USA

    Motonari Uesugi

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  1. James R Jabbur
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  2. Amy D Tabor
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  4. Hua Wang
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  6. Guillermina Lozano
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  7. Wei Zhang
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Correspondence to Wei Zhang.

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Jabbur, J., Tabor, A., Cheng, X. et al. Mdm-2 binding and TAFII31 recruitment is regulated by hydrogen bond disruption between the p53 residues Thr18 and Asp21. Oncogene 21, 7100–7113 (2002). https://doi.org/10.1038/sj.onc.1205856

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