A novel cervical cancer suppressor 3 (CCS-3) interacts with the BTB domain of PLZF and inhibits the cell growth by inducing apoptosis.

Promyelocytic leukemia zinc finger protein (PLZF) is a sequence-specific, DNA binding, transcriptional repressor differentially expressed during embryogenesis and in adult tissues. PLZF is known to be a negative regulator of cell cycle progression. We used PLZF as bait in a yeast two-hybrid screen with a cDNA library from the human ...
ovary tissue. A novel cervical cancer suppressor 3 (CCS-3) was identified as a PLZF interacting partner. Further characterization revealed the BTB domain as an interacting domain of PLZF. Interaction of CCS-3 with PLZF in mammalian cells was also confirmed by co-immunoprecipitation and in vitro binding assays. It was found that, although CCS-3 shares similar homology with eEF1A, the study determined CCS-3 to be an isoform. CCS-3 was observed to be downregulated in human cervical cell lines as well as in cervical tumors when compared to those from normal tissues. Overexpression of CCS-3 in human cervical cell lines inhibits cell growth by inducing apoptosis and suppressing human cyclin A2 promoter activity. These combined results suggest that the potential tumor suppressor activity of CCS-3 may be mediated by its interaction with PLZF.
Mesh Terms:
Apoptosis, Cyclin A, Cyclin A2, DNA-Binding Proteins, Embryonic Development, Female, Gene Expression Regulation, Neoplastic, Hela Cells, Humans, Kruppel-Like Transcription Factors, Ovary, Peptide Elongation Factor 1, Promoter Regions, Genetic, Protein Binding, Protein Isoforms, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Transcription Factors, Tumor Suppressor Proteins, Two-Hybrid System Techniques, Uterine Cervical Neoplasms
FEBS Lett.
Date: Jul. 24, 2006
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