title: Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells.
abstract: 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 ER transactivation 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.
authors: Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Suresh K
authors: SK
authors: Rayala
authors: Petra
authors: P
authors: den Hollander
authors: Bramanandam
authors: B
authors: Manavathi
authors: Amjad H
authors: AH
authors: Talukder
authors: Chunying
authors: C
authors: Song
authors: Shaohua
authors: S
authors: Peng
authors: Angelika
authors: A
authors: Barnekow
authors: Joachim
authors: J
authors: Kremerskothen
authors: Rakesh
authors: R
authors: Kumar