Essential Role of KIBRA in Co-activator Function of Dynein Light Chain 1 in Mammalian Cells
Autor: | Amjad H. Talukder, Bramanandam Manavathi, Joachim Kremerskothen, Petra den Hollander, Rakesh Kumar, Shaohua Peng, Angelika Barnekow, Suresh K. Rayala, Chunying Song |
---|---|
Rok vydání: | 2006 |
Předmět: |
Cytoplasmic Dyneins
Transcriptional Activation Dynein Glutamic Acid Estrogen receptor Biochemistry Histones WW domain Histone H3 Transactivation Cell Line Tumor Humans Cloning Molecular Promoter Regions Genetic Cytoskeleton Molecular Biology biology Estrogen Receptor alpha Intracellular Signaling Peptides and Proteins Dyneins Proteins Cell Biology Phosphoproteins Chromatin Protein Structure Tertiary Cell biology biology.protein DLC1 Protein Binding |
Zdroj: | Journal of Biological Chemistry. 281:19092-19099 |
ISSN: | 0021-9258 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |