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PMID:15328371

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Citation

Wang, W, Nahta, R, Huper, G and Marks, JR (2004) TAFII70 isoform-specific growth suppression correlates with its ability to complex with the GADD45a protein. Mol. Cancer Res. 2:442-52

Abstract

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.

Links

PubMed

Keywords

Amino Acid Sequence; Animals; Breast Neoplasms/genetics; Breast Neoplasms/metabolism; Breast Neoplasms/pathology; Cell Cycle Proteins/metabolism; Cell Line; Cell Proliferation; Gene Expression; Humans; Mice; Molecular Sequence Data; Mutation/genetics; Nuclear Proteins/metabolism; Protein Binding; Protein Isoforms/chemistry; Protein Isoforms/deficiency; Protein Isoforms/genetics; Protein Isoforms/metabolism; TATA-Binding Protein Associated Factors; Transcription Factors/chemistry; Transcription Factors/deficiency; Transcription Factors/genetics; Transcription Factors/metabolism; Transcription, Genetic/genetics; Tumor Suppressor Protein p53/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:GA45A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P49848

F

Seeded From UniProt

complete

HUMAN:TAF6

enables

GO:0016251: RNA polymerase II general transcription initiation factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:TAF6

involved_in

GO:0006367: transcription initiation from RNA polymerase II promoter

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TAF6

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P24522

F

Seeded From UniProt

complete

HUMAN:TAF6

involved_in

GO:0045786: negative regulation of cell cycle

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TAF6

involved_in

GO:0008285: negative regulation of cell population proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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