Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells.
Rayala SK, den Hollander P, Manavathi B, Talukder AH, Song C, Peng S, Barnekow A, Kremerskothen J, Kumar R
Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Recently dynein light chain 1 (DLC1 [?]), a cytoskeleton signaling component, has been shown to interact with and transactivate estrogen receptor-alpha (ER), leading to increased expression of ER target genes and growth stimulation of breast cancer cells. However, the molecular mechanism by which DLC1 [?] regulates the ER pathway remains poorly understood. To gain insights into the putative mechanism, here we set out to identify novel DLC1 [?]-interacting proteins. We identified KIBRA, a WW domain- and a glutamic acid [?] stretch-containing protein, as a DLC1 [?]-binding protein and showed that it interacts with DLC1 [?] both in vitro and in vivo. We found that KIBRA-DLC1 [?] complex is recruited to ER-responsive promoters. We also found that KIBRA-DLC1 [?] interaction is mandatory for the recruitment and transactivation functions of ER or DLC1 [?] to the target chromatin. Finally we found that KIBRA interacts with histone H3 via its glutamic acid [?]-rich region and that such interaction might play a mechanistic role in conferring an optimal ERtransactivation function as well as the proliferation of ligand-stimulated breast cancer cells. Together these findings indicate that DLC1 [?]-KIBRA interaction is essential for ER transactivation in breast cancer cells.
J. Biol. Chem. (2006)
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