MTA1, a transcriptional activator of breast cancer amplified sequence 3
(2006) In Proceedings of the National Academy of Sciences 103(17). p.6670-6675- Abstract
- Here we define a function of metastasis-associated protein 1 (MTA1), a presumed corepressor of estrogen receptor alpha (ER alpha), as a transcriptional activator of Breast Cancer Amplified Sequence 3 (BCAS3), a gene amplified and overexpressed in breast cancers. We identified BCAS3 as a MTA1 chromatin target in a functional genomic screen. MTA1 stimulation of BCAS3 transcription required ERa and involved a functional ERE half-site in BCAS3. Furthermore, we discovered that MTA1 is acetylated on lysine 626, and that this acetylation is necessary for a productive transcriptional recruitment of RNA polymerase 11 complex to the BCAS3 enhancer sequence. BCAS3 expression was elevated in mammary tumors from MTA1 transgenic mice and 60% of the... (More)
- Here we define a function of metastasis-associated protein 1 (MTA1), a presumed corepressor of estrogen receptor alpha (ER alpha), as a transcriptional activator of Breast Cancer Amplified Sequence 3 (BCAS3), a gene amplified and overexpressed in breast cancers. We identified BCAS3 as a MTA1 chromatin target in a functional genomic screen. MTA1 stimulation of BCAS3 transcription required ERa and involved a functional ERE half-site in BCAS3. Furthermore, we discovered that MTA1 is acetylated on lysine 626, and that this acetylation is necessary for a productive transcriptional recruitment of RNA polymerase 11 complex to the BCAS3 enhancer sequence. BCAS3 expression was elevated in mammary tumors from MTA1 transgenic mice and 60% of the human breast tumors, and correlated with the coexpression of MTA1 as well as with tumor grade and proliferation of primary breast tumor samples. These findings reveal a previously unrecognized function of MTA1 in stimulating BCAS3 expression and suggest an important role for MTA1-BCAS3 pathway in promoting cancerous phenotypes in breast tumor cells. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/410255
- author
- Gururaj, AE ; Singh, RR ; Rayala, SK ; Wigerup, Caroline LU ; den Hollander, P ; Zhang, H ; Balasenthil, S ; Talukder, AH ; Landberg, Göran LU and Kumar, R
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- estrogen receptor, BCAS3, coactivator
- in
- Proceedings of the National Academy of Sciences
- volume
- 103
- issue
- 17
- pages
- 6670 - 6675
- publisher
- National Academy of Sciences
- external identifiers
-
- pmid:16617102
- wos:000237151000046
- scopus:33646238716
- pmid:16617102
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.0601989103
- language
- English
- LU publication?
- yes
- id
- 4d2badf6-1890-408d-8b5f-abad52f4c4b3 (old id 410255)
- date added to LUP
- 2016-04-01 11:35:48
- date last changed
- 2022-05-06 06:20:51
@article{4d2badf6-1890-408d-8b5f-abad52f4c4b3, abstract = {{Here we define a function of metastasis-associated protein 1 (MTA1), a presumed corepressor of estrogen receptor alpha (ER alpha), as a transcriptional activator of Breast Cancer Amplified Sequence 3 (BCAS3), a gene amplified and overexpressed in breast cancers. We identified BCAS3 as a MTA1 chromatin target in a functional genomic screen. MTA1 stimulation of BCAS3 transcription required ERa and involved a functional ERE half-site in BCAS3. Furthermore, we discovered that MTA1 is acetylated on lysine 626, and that this acetylation is necessary for a productive transcriptional recruitment of RNA polymerase 11 complex to the BCAS3 enhancer sequence. BCAS3 expression was elevated in mammary tumors from MTA1 transgenic mice and 60% of the human breast tumors, and correlated with the coexpression of MTA1 as well as with tumor grade and proliferation of primary breast tumor samples. These findings reveal a previously unrecognized function of MTA1 in stimulating BCAS3 expression and suggest an important role for MTA1-BCAS3 pathway in promoting cancerous phenotypes in breast tumor cells.}}, author = {{Gururaj, AE and Singh, RR and Rayala, SK and Wigerup, Caroline and den Hollander, P and Zhang, H and Balasenthil, S and Talukder, AH and Landberg, Göran and Kumar, R}}, issn = {{1091-6490}}, keywords = {{estrogen receptor; BCAS3; coactivator}}, language = {{eng}}, number = {{17}}, pages = {{6670--6675}}, publisher = {{National Academy of Sciences}}, series = {{Proceedings of the National Academy of Sciences}}, title = {{MTA1, a transcriptional activator of breast cancer amplified sequence 3}}, url = {{http://dx.doi.org/10.1073/pnas.0601989103}}, doi = {{10.1073/pnas.0601989103}}, volume = {{103}}, year = {{2006}}, }