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This work was supported by Cancer Research UK Grants C11509/A8570 and C11509/A12426 and Ministerio de Ciencia e Innovacion Grants SAF2007-62642 and SAF2010-21013.

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Belandia, BorjaAuthor

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May 17, 2023
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Repression of Androgen Receptor Activity by HEYL, a Third Member of the Hairy/Enhancer-of-split-related Family of Notch Effectors

Publicated to:JOURNAL OF BIOLOGICAL CHEMISTRY. 286 (20): 17796-17808 - 2011-05-20 286(20), DOI: 10.1074/jbc.M110.198655

Authors: Lavery, DN; Villaronga, MA; Walker, MM; Patel, A; Belandia, B; Bevan, CL

Affiliations

Imperial Coll Healthcare Trust, St Marys Hosp, Dept Urol, London W2 1NY, England - Author
Univ Autonoma Madrid, CSIC, Inst Invest Biomed Alberto Sols, Dept Canc Biol, Madrid 28029, Spain - Author
Univ London Imperial Coll Sci Technol & Med, Ctr Pathol, Div Med, London W2 1NY, England - Author
Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, Androgen Signalling Lab, London W12 0NN, England - Author

Abstract

The Hairy/Enhancer-of-split-related with YRPW-like motif (HEY) family of proteins are transcriptional repressors and downstream effectors of Notch signaling. We previously reported that HEY1 and HEY2 selectively repress androgen receptor (AR) signaling in mammalian cell lines and have shown that in human tissue HEY1 is excluded from the nuclei in prostate cancer but not benign prostatic hyperplasia. We have now characterized a third member of this family, HEYL, which is a more potent repressor of AR activity. HEYL interacted with and repressed AR activation function-1 domain and competitively inhibited SRC1e activation of AR transcriptional activity. Using a cell line inducibly expressing exogenous HEYL, we showed that HEYL represses endogenous AR-regulated genes and reduces androgen-dependent prostate cancer cell growth. Using a transrepression assay, we identified both trichostatin-sensitive and -insensitive domains within HEYL; however, analysis of endogenous AR target genes suggested that HEYL represses AR activity through histone deacetylase I/II-independent mechanisms. Immunohistochemical analyses of tissue indicated that, in a fashion similar to that previously reported for HEY1, HEYL is excluded from the nuclei in prostate cancer but not adjacent benign tissue. This suggests that nuclear exclusion of HEY proteins may be an important step in the progression of prostate cancer.

Keywords

Cofactor p44CorepressorCyclin d1DomainGene-expressionNuclearProliferationProstate-cancerTargetTranscriptional activation

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal JOURNAL OF BIOLOGICAL CHEMISTRY due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2011, it was in position 66/290, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biochemistry & Molecular Biology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 4.49, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-18, the following number of citations:

  • WoS: 34

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-18:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 28 (PlumX).

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: United Kingdom.