Title: A temperature-sensitive mutant of human p53.
Abstract: Research Article1 June 1994free access A temperature-sensitive mutant of human p53. W. Zhang W. Zhang Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030. Search for more papers by this author X.Y. Guo X.Y. Guo Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030. Search for more papers by this author G.Y. Hu G.Y. Hu Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030. Search for more papers by this author W.B. Liu W.B. Liu Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030. Search for more papers by this author J.W. Shay J.W. Shay Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030. Search for more papers by this author A.B. Deisseroth A.B. Deisseroth Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030. Search for more papers by this author W. Zhang W. Zhang Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030. Search for more papers by this author X.Y. Guo X.Y. Guo Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030. Search for more papers by this author G.Y. Hu G.Y. Hu Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030. Search for more papers by this author W.B. Liu W.B. Liu Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030. Search for more papers by this author J.W. Shay J.W. Shay Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030. Search for more papers by this author A.B. Deisseroth A.B. Deisseroth Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030. Search for more papers by this author Author Information W. Zhang1, X.Y. Guo1, G.Y. Hu1, W.B. Liu1, J.W. Shay1 and A.B. Deisseroth1 1Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030. The EMBO Journal (1994)13:2535-2544https://doi.org/10.1002/j.1460-2075.1994.tb06543.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info We discovered that the human ‘hot-spot’ p53 mutant 143Ala is temperature sensitive for the binding of two DNA elements and for mediating the transcription of a downstream luciferase reporter gene. At 32.5 degrees C, 143Ala possesses strong DNA binding ability. In addition, its transcriptional activities are stronger than those of wild-type p53. At 37.5 degrees C, however, both the mutant's DNA binding and transcriptional activation functions are greatly reduced or abolished. The activity differences correlate with the presence of two conformational states of p53, which are recognized by monoclonal antibodies: at 32.5 degrees C, 143Ala is recognized by PAb1620, which is specific for the wild-type conformation, whereas at 37.5 degrees C, 143Ala is almost undetectable by PAb1620-mediated immunoprecipitation. Although 143Ala's binding to p53 DNA recognition elements and its activation of reporter gene transcription at 32.5 degrees C is markedly higher than that of the wild-type p53, 143Ala inhibited proliferation less robustly than wild-type p53 and it did not increase inhibition of ras-induced focus formation. These results indicate a partial correlation between the events involved in transcriptional activation and events involved in the proliferation suppression of p53. 143Ala therefore will be of use in dissecting the relationship between the structure of p53 and its different cellular functions. Previous ArticleNext Article Volume 13Issue 111 June 1994In this issue RelatedDetailsLoading ...