Functional regulation of oestrogen receptor pathway by the dynein light chain 1.
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.
Rayala
Suresh K
SK
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
den Hollander
Petra
P
Balasenthil
Seetharaman
S
Yang
Zhibo
Z
Broaddus
Russell R
RR
Kumar
Rakesh
R
D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D056445:Cytoplasmic Dyneins; D004305:Dose-Response Relationship, Drug; D004398:Dyneins / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D002843:Chromatin; D004967:Estrogens; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; C427758:DYNLL1 protein, human; D056445:Cytoplasmic Dyneins; D004398:Dyneins