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Functional regulation of oestrogen receptor pathway by the dynein light chain 1
Author(s) -
Rayala Suresh K,
den Hollander Petra,
Balasenthil Seetharaman,
Yang Zhibo,
Broaddus Russell R,
Kumar Rakesh
Publication year - 2005
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400417
Subject(s) - transactivation , downregulation and upregulation , microbiology and biotechnology , nuclear receptor , biology , estrogen receptor , phosphorylation , estrogen receptor alpha , cancer research , chemistry , transcription factor , gene , breast cancer , biochemistry , genetics , cancer
Overexpression and phosphorylation of dynein light chain 1 (DLC1) have been shown to promote the growth of breast cancer cells. However, the role of DLC1 in the action of the oestrogen receptor (ER) remains unknown. Here, we found that oestrogen induces the transcription and expression of DLC1. DLC1 facilitated oestrogen‐induced ER transactivation and anchorage‐independent growth of breast cancer cells. We show that DLC1 interacts with ER, and such interaction is required for the transactivation‐promoting activity of DLC1. Further, DLC1 expression led to enhanced recruitment of the DLC1–ER complex to the ER‐target gene chromatin. Conversely, DLC1 downregulation compromised the ER‐transactivation activity and also its nuclear accumulation, suggesting a potential chaperone‐like activity of DLC1 in the nuclear translocation of ER. Together, these data define an unexpected upregulation of DLC1 by oestrogen and a previously unrecognized DLC1–ER interaction in supporting and amplifying ER‐initiated cellular responses in breast cancer cells.