TAFII70 isoform-specific growth suppression correlates with its ability to complex with the GADD45a protein.
TAFII70, a member of the basal transcription complex implicated in p53-mediated transcription, is synthesized as several alternately spliced variants. The predominant forms found in normal and neoplastic breast epithelial cells are shown to be 72 kDa (TAFII70) and 78 kDa (TAFII80). Most cancers express higher levels of the TAFII80 isoform, whereas normal breast epithelia express higher levels of the TAFII70 isoform. Expression of TAFII70, but not TAFII80, causes dramatic growth suppression of normal and transformed breast epithelial cell lines in a p53-independent manner. Growth suppression correlates with mitotic inhibition resulting from an increased number of cells in G2. Both isoforms induce expression of the G2 arrest associated gene, GADD45a, but a novel protein-protein interaction was observed between TAFII70 (not TAFII80) and GADD45a, suggesting that this interaction is important for the observed growth arrest phenotype induced by the TAFII70 isoform. GADD45a null cells are not subject to TAFII70 inhibition, further supporting the relevance of this interaction.
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Wei
W
Wang
Rita
R
Nahta
Gudrun
G
Huper
Jeffrey R
JR
Marks
D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D035381:TATA-Binding Protein Associated Factors; D014157:Transcription Factors / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D000097642:GADD45 Proteins
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D035381:TATA-Binding Protein Associated Factors; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C499072:Gadd45a protein, mouse; C084977:TAF6 protein, human