Regulation of HSF1-responsive gene expression by N-terminal truncated form of p73alpha.
DNp73 is a transactivation domain (TAD)-truncated form of p73. The ability of DNp73alpha to regulate gene expression was examined using reporter assays with luciferase gene constructs. Among various promoter-regulated reporter genes tested, heat shock factor (HSF)-responsive gene expression was selectively activated by DNp73alpha, but not by other p73-isoforms with TAD and DNp73beta. Deletion of TAD endowed p73alpha with the ability to activate HSF-responsive gene expression, but deletion of N-terminal proline-rich domain (PRD) rendered both DNp73alpha and the TAD-deleted p73alpha inactive. Considering the inability of DNp73beta, which is the C-terminus-truncated form of DNp73alpha, to function, these results indicate that both the PRD and C-terminus are necessary for DNp73alpha to be able to activate the HSF-dependent gene expression. In addition to the reporter gene expression, both DNp73alpha and TAD-deleted p73alpha activated the expression of an endogenous gene, hsp70, corresponding with an increase in the active form of HSF1. Taken together, these results demonstrate that TAD-truncated p73alpha can activate HSF-dependent gene expression via induction of active HSF1.
Tanaka
Yasuharu
Y
Department of Biochemistry, Nara Medical University, Shijo-Cho 840, Kashihara, Nara 634-8521, Japan. ytanaka@naramed-u.ac.jp
Kameoka
Masanori
M
Itaya
Asako
A
Ota
Katsuya
K
Yoshihara
Koichiro
K
D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D000076249:Heat Shock Transcription Factors; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology*; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D017931:DNA Primers; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins