The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity
Publication Year 2002-03-08, Volume 277, Issue #10, Page 7849-7856
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Publication Type
- Journal Article
- LMO4 belongs to the LIM-only (LMO) group of transcriptional regulators that appear to function as molecular adaptors for protein-protein interactions. Expression of the LMO4 gene is developmentally regulated in the mammary gland and is up-regulated in primary breast cancers. Using LMO4 in a yeast two-hybrid screen, we have identified the cofactor CtIP as an LMO4-binding protein. Interaction with CtIP appeared to be specific for the LMO subclass of LIM domain proteins and could be mediated by a single LIM motif of LMO4. We further identified the breast tumor suppressor BRCA1 as an LMO4-associated protein. The C-terminal BRCT domains of BRCA1, previously shown to bind CtIP, also mediated interaction with LMO4. Tumor-associated mutations within the BRCT repeats that abolish interaction between BRCA1 and CtIP had no effect on the association of BRCA1 with LMO4. A stable complex comprising LMO4, BRCA1, and CtIP was demonstrated in vivo. The LIM domain binding-protein Ldb1 also participated in this multiprotein complex. In functional assays, LMO4 was shown to repress BRCA1-mediated transcriptional activation in both yeast and mammalian cells. These findings reveal a novel complex between BRCA1, LMO4, and CtIP and indicate a role for LMO4 as a repressor of BRCA1 activity in breast tissue.
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- SPORADIC BREAST-CANCER; LOOP-HELIX PROTEIN; C-TERMINAL REGION; T-CELL LEUKEMIA; TRANSCRIPTIONAL ACTIVATION; BINDING-PROTEIN; OVARIAN-CANCER; HOMEODOMAIN PROTEINS; SUSCEPTIBILITY GENE; MOLECULAR-CLONING
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Creation Date: 2002-03-08 12:00:00Last Modified: 0001-01-01 12:00:00