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      • Record: found
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      Small leucine zipper protein functions as a negative regulator of estrogen receptor α in breast cancer

      research-article
      Author(s): , , , , *
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      Publication date (Electronic):
      Journal: PLoS ONE
      Publisher: Public Library of Science

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          Abstract

          The nuclear transcription factor estrogen receptor α (ERα) plays a critical role in breast cancer progression. ERα acts as an important growth stimulatory protein in breast cancer and the expression level of ERα is tightly related to the prognosis and treatment of patients. Small leucine zipper protein (sLZIP) functions as a transcriptional cofactor by binding to various nuclear receptors, including glucocorticoid receptor, androgen receptor, and peroxisome proliferator-activated receptor γ. However, the role of sLZIP in the regulation of ERα and its involvement in breast cancer progression is unknown. We found that sLZIP binds to ERα and represses the transcriptional activity of ERα in ERα-positive breast cancer cells. sLZIP also suppressed the expression of ERα target genes. sLZIP disrupted the binding of ERα to the estrogen response element of the target gene promoter, resulting in suppression of cell proliferation. sLZIP is a novel co-repressor of ERα, and plays a negative role in ERα-mediated cell proliferation in breast cancer.

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          Most cited references29

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          The nuclear receptor superfamily: the second decade.

          D J Mangelsdorf, C Thummel, M. Beato … (1995)
          Article 0 comments Cited 368 times – based on 0 reviews     Review now
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            Estrogen receptors and human disease.

            Bonnie J. Deroo, Kenneth S. Korach (2006)
            Estrogens influence many physiological processes in mammals, including but not limited to reproduction, cardiovascular health, bone integrity, cognition, and behavior. Given this widespread role for estrogen in human physiology, it is not surprising that estrogen is also implicated in the development or progression of numerous diseases, which include but are not limited to various types of cancer (breast, ovarian, colorectal, prostate, endometrial), osteoporosis, neurodegenerative diseases, cardiovascular disease, insulin resistance, lupus erythematosus, endometriosis, and obesity. In many of these diseases, estrogen mediates its effects through the estrogen receptor (ER), which serves as the basis for many therapeutic interventions. This Review will describe diseases in which estrogen, through the ER, plays a role in the development or severity of disease.
            Article 0 comments Cited 306 times – based on 0 reviews     Review now
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              A signature motif in transcriptional co-activators mediates binding to nuclear receptors.

              D Heery, E Kalkhoven, S. Hoare … (1997)
              The binding of lipophilic hormones, retinoids and vitamins to members of the nuclear-receptor superfamily modifies the DNA-binding and transcriptional properties of these receptors, resulting in the activation or repression of target genes. Ligand binding induces conformational changes in nuclear receptors and promotes their association with a diverse group of nuclear proteins, including SRC-1/p160, TIF-2/GRIP-1 and CBP/p300 which function as co-activators of transcription, and RIP-140, TIF-1 and TRIP-1/SUG-1 whose functions are unclear. Here we report that a short sequence motif LXXLL (where L is leucine and X is any amino acid) present in RIP-140, SRC-1 and CBP is necessary and sufficient to mediate the binding of these proteins to liganded nuclear receptors. We show that the ability of SRC-1 to bind the oestrogen receptor and enhance its transcriptional activity is dependent upon the integrity of the LXXLL motifs and on key hydrophobic residues in a conserved helix (helix 12) of the oestrogen receptor that are required for its ligand-induced activation function. We propose that the LXXLL motif is a signature sequence that facilitates the interaction of different proteins with nuclear receptors, and is thus a defining feature of a new family of nuclear proteins.
              Article 0 comments Cited 266 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Gokul M. Das: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 29 June 2017
                Publication date Collection: 2017
                Volume: 12
                Issue: 6
                Electronic Location Identifier: e0180197
                Affiliations
                [001]Division of Life Sciences, Korea University, Seoul, South Korea
                Roswell Park Cancer Institute, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: JK.

                • Data curation: JJ SP.

                • Formal analysis: JJ SP.

                • Funding acquisition: JK.

                • Investigation: JJ SP H-TA MK.

                • Methodology: JJ SP JK.

                • Project administration: JK.

                • Supervision: JK.

                • Validation: JK.

                • Visualization: JJ SP JK.

                • Writing – original draft: JJ SP.

                • Writing – review & editing: JK.

                Article
                Publisher ID: PONE-D-16-48148
                DOI: 10.1371/journal.pone.0180197
                PMC ID: 5491147
                PubMed ID: 28662179
                SO-VID: 78bf5e73-33db-4356-bdd5-42ef0836b9ff
                Copyright © © 2017 Jeong et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 5 December 2016
                Date accepted : 12 June 2017
                Page count
                Figures: 4, Tables: 0, Pages: 12
                Funding
                This work was supported by Tunneling Nanotube Research Center (NRF-2015R1A5A1009024) through the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP).
                Categories
                Subject: Research Article
                Subject: Medicine and Health Sciences
                Subject: Oncology
                Subject: Cancers and Neoplasms
                Subject: Breast Tumors
                Subject: Breast Cancer
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Hormones
                Subject: Estrogens
                Subject: Biology and Life Sciences
                Subject: Genetics
                Subject: Gene Expression
                Subject: Gene Regulation
                Subject: Research and Analysis Methods
                Subject: Precipitation Techniques
                Subject: Immunoprecipitation
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cell Processes
                Subject: Cell Proliferation
                Subject: Biology and life sciences
                Subject: Genetics
                Subject: Gene expression
                Subject: Gene regulation
                Subject: Small interfering RNAs
                Subject: Biology and life sciences
                Subject: Biochemistry
                Subject: Nucleic acids
                Subject: RNA
                Subject: Non-coding RNA
                Subject: Small interfering RNAs
                Subject: Biology and Life Sciences
                Subject: Genetics
                Subject: Gene Expression
                Subject: Biology and life sciences
                Subject: Biochemistry
                Subject: Proteins
                Subject: DNA-binding proteins
                Subject: Transcription Factors
                Subject: Biology and Life Sciences
                Subject: Genetics
                Subject: Gene Expression
                Subject: Gene Regulation
                Subject: Transcription Factors
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Proteins
                Subject: Regulatory Proteins
                Subject: Transcription Factors
                Custom metadata
                Data Availability All relevant data are within the paper.

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

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