BRCA1 transactivates the cyclin-dependent kinase inhibitor p27Kip1

Elizabeth A. Williamson; Farnaz Dadmanesh; H. Phillip Koeffler

doi:10.1038/sj.onc.1205461

BRCA1 transactivates the cyclin-dependent kinase inhibitor p27^Kip1

Elizabeth A. Williamson
, Farnaz Dadmanesh
, H. Phillip Koeffler

Research output: Contribution to journal › Article › peer-review

54 Scopus citations

Abstract

The p27^Kip1 is a member of the universal cyclin-dependent kinase inhibitor family. Previously, immunochemical analysis of a series of breast cancer cell lines demonstrated a correlation between the expression of p27^Kip1 and the breast cancer susceptibility gene BRCA1. BRCA1 has a number of activities including DNA repair, growth inhibition and as a transcription factor. Here we demonstrate that BRCA1 transactivates expression of p27^Kip1. This transactivation is dependent on the presence of a functional C-terminal transactivation domain. Promoter-deletion analysis identified the presence of a putative BRCA1-responsive element located at position -615 to -511 of the p27^Kip1 promoter. These results suggest that the transcriptional regulation of p27^Kip1 by BRCA1 may be a mechanism for BRCA1- induced growth inhibition.

Original language	English (US)
Pages (from-to)	3199-3206
Number of pages	8
Journal	Oncogene
Volume	21
Issue number	20
DOIs	https://doi.org/10.1038/sj.onc.1205461
State	Published - May 9 2002
Externally published	Yes

Keywords

BRCA1
P27
Transcriptional regulation

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

Access to Document

10.1038/sj.onc.1205461

Cite this

@article{3bc6f7efbfe54a89ab13fc060e78ba60,

title = "BRCA1 transactivates the cyclin-dependent kinase inhibitor p27Kip1",

abstract = "The p27Kip1 is a member of the universal cyclin-dependent kinase inhibitor family. Previously, immunochemical analysis of a series of breast cancer cell lines demonstrated a correlation between the expression of p27Kip1 and the breast cancer susceptibility gene BRCA1. BRCA1 has a number of activities including DNA repair, growth inhibition and as a transcription factor. Here we demonstrate that BRCA1 transactivates expression of p27Kip1. This transactivation is dependent on the presence of a functional C-terminal transactivation domain. Promoter-deletion analysis identified the presence of a putative BRCA1-responsive element located at position -615 to -511 of the p27Kip1 promoter. These results suggest that the transcriptional regulation of p27Kip1 by BRCA1 may be a mechanism for BRCA1- induced growth inhibition.",

keywords = "BRCA1, P27, Transcriptional regulation",

author = "Williamson, \{Elizabeth A.\} and Farnaz Dadmanesh and Koeffler, \{H. Phillip\}",

note = "Funding Information: We thank B Weber, J Holt, J Wyke and T Sakai for the BRCA1 and p27Kip1 promoter constructs. EA Williamson is a recipient of a Postdoctoral Fellowship from the California Breast Cancer Research Program. HP Koe‚er holds the endowed Mark Goodsen Chair of Oncology and is a member of the Jonsson Cancer Center. This work was supported by the Ko-So Foundation and the Parker Hughes Trust. We are grateful for the generous support of Norma Thorworth's Fund.",

year = "2002",

month = may,

day = "9",

doi = "10.1038/sj.onc.1205461",

language = "English (US)",

volume = "21",

pages = "3199--3206",

journal = "Oncogene",

issn = "0950-9232",

publisher = "Springer Nature",

number = "20",

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TY - JOUR

T1 - BRCA1 transactivates the cyclin-dependent kinase inhibitor p27Kip1

AU - Williamson, Elizabeth A.

AU - Dadmanesh, Farnaz

AU - Koeffler, H. Phillip

N1 - Funding Information: We thank B Weber, J Holt, J Wyke and T Sakai for the BRCA1 and p27Kip1 promoter constructs. EA Williamson is a recipient of a Postdoctoral Fellowship from the California Breast Cancer Research Program. HP Koe‚er holds the endowed Mark Goodsen Chair of Oncology and is a member of the Jonsson Cancer Center. This work was supported by the Ko-So Foundation and the Parker Hughes Trust. We are grateful for the generous support of Norma Thorworth's Fund.

PY - 2002/5/9

Y1 - 2002/5/9

N2 - The p27Kip1 is a member of the universal cyclin-dependent kinase inhibitor family. Previously, immunochemical analysis of a series of breast cancer cell lines demonstrated a correlation between the expression of p27Kip1 and the breast cancer susceptibility gene BRCA1. BRCA1 has a number of activities including DNA repair, growth inhibition and as a transcription factor. Here we demonstrate that BRCA1 transactivates expression of p27Kip1. This transactivation is dependent on the presence of a functional C-terminal transactivation domain. Promoter-deletion analysis identified the presence of a putative BRCA1-responsive element located at position -615 to -511 of the p27Kip1 promoter. These results suggest that the transcriptional regulation of p27Kip1 by BRCA1 may be a mechanism for BRCA1- induced growth inhibition.

AB - The p27Kip1 is a member of the universal cyclin-dependent kinase inhibitor family. Previously, immunochemical analysis of a series of breast cancer cell lines demonstrated a correlation between the expression of p27Kip1 and the breast cancer susceptibility gene BRCA1. BRCA1 has a number of activities including DNA repair, growth inhibition and as a transcription factor. Here we demonstrate that BRCA1 transactivates expression of p27Kip1. This transactivation is dependent on the presence of a functional C-terminal transactivation domain. Promoter-deletion analysis identified the presence of a putative BRCA1-responsive element located at position -615 to -511 of the p27Kip1 promoter. These results suggest that the transcriptional regulation of p27Kip1 by BRCA1 may be a mechanism for BRCA1- induced growth inhibition.

KW - BRCA1

KW - P27

KW - Transcriptional regulation

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DO - 10.1038/sj.onc.1205461

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