Role of GIF1 (GADD45 Interacting Factor 1) in Breast Cancer
Abstract
Gadd45, a DNA damage inducible gene, plays role(s) in DNA repair and regulation of cell proliferation. Using yeast two hybrid system, we identified a novel gene whose products interact with GADD45 alpha and named it as GIF1 (Gadd45 alpha Interacting Factor 1). Alternative name of GIF1 is CRIF1 (=CR6 interacting factor 1, CR6=Gadd45 gamma). During the first year of finding period, we reported that a physical interaction of Gadd45 family proteins and GIF1 in mammalian cells using IP and GST pulldown assay. In the same paper, we also reported that GIF1 inhibits the cyclin-dependent kinases, Cdc2/cyclin Bl kinase and Cdk2/cyclin E, so it renders inhibition of the cell cycle progression at the G1/S phase and suppresses growth in serum stimulated NIH3T3 cells. In order to introduce GIF1 efficiently into breast cancer cells, we constructed rAd-GIF and confirmed that exogenous GIF expression in breast cancer cell lines. Infection of rAd-GIF1 increased cells in G1 phase in human cells. To extend our study we performed another round of yeast hybrid screening and found GIF interact with two other nuclear hormone receptor, NUR77 and Androgen receptor. We submitted a manuscript titled as "CR6 Interacting Factor 1 (CRIF1) inhibits with Orphan Nuclear Receptor Nur77 and inhibits its transactivation". Before initiating Task3 (role of GIF1 in response to cytotoxic agents), we examined whether GIF1 mRNA is inducible in response to stress such as X-ray, MMS, UVB, H2O2, ADR (adriamycin), Thapsigargin, Taxol, Camptothecin, Cis-Platinurn, TPA, Nacl, Heat shock, Arsenic in TK6 (p53wt), NH32 (p53 KO) and MCF-7 breast cancer cells. In this experiments we concluded that GIF1 is not a stress inducible gene.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA428560
Entities
People
- Insoo Bae
Organizations
- Georgetown University