Title: Prolyl isomerase Pin1 negatively regulates the stability of SUV39H1 to promote tumorigenesis in breast cancer
Abstract: The FASEB JournalVolume 27, Issue 11 p. 4606-4618 Research CommunicationFree to Read Prolyl isomerase Pin1 negatively regulates the stability of SUV39H1 to promote tumorigenesis in breast cancer Prem Khanal, Prem Khanal College of Pharmacy, Chosun University, Gwangju, South Korea These authors contributed equally to this work.Search for more papers by this authorGaram Kim, Garam Kim College of Pharmacy, Chosun University, Gwangju, South Korea These authors contributed equally to this work.Search for more papers by this authorSung-Chul Lim, Sung-Chul Lim Department of Pathology, School of Medicine, Chosun University, Gwangju, South KoreaSearch for more papers by this authorHyo-Jeong Yun, Hyo-Jeong Yun College of Pharmacy, Chosun University, Gwangju, South KoreaSearch for more papers by this authorKwang Youl Lee, Kwang Youl Lee College of Pharmacy, Chonnam National University, Gwangju, South KoreaSearch for more papers by this authorHoo-Kyun Choi, Hoo-Kyun Choi College of Pharmacy, Chosun University, Gwangju, South KoreaSearch for more papers by this authorHong Seok Choi, Corresponding Author Hong Seok Choi [email protected] College of Pharmacy, Chosun University, Gwangju, South KoreaCorrespondence: College of Pharmacy, Chosun University, Gwangju 501-759, South Korea. E-mail: [email protected] for more papers by this author Prem Khanal, Prem Khanal College of Pharmacy, Chosun University, Gwangju, South Korea These authors contributed equally to this work.Search for more papers by this authorGaram Kim, Garam Kim College of Pharmacy, Chosun University, Gwangju, South Korea These authors contributed equally to this work.Search for more papers by this authorSung-Chul Lim, Sung-Chul Lim Department of Pathology, School of Medicine, Chosun University, Gwangju, South KoreaSearch for more papers by this authorHyo-Jeong Yun, Hyo-Jeong Yun College of Pharmacy, Chosun University, Gwangju, South KoreaSearch for more papers by this authorKwang Youl Lee, Kwang Youl Lee College of Pharmacy, Chonnam National University, Gwangju, South KoreaSearch for more papers by this authorHoo-Kyun Choi, Hoo-Kyun Choi College of Pharmacy, Chosun University, Gwangju, South KoreaSearch for more papers by this authorHong Seok Choi, Corresponding Author Hong Seok Choi [email protected] College of Pharmacy, Chosun University, Gwangju, South KoreaCorrespondence: College of Pharmacy, Chosun University, Gwangju 501-759, South Korea. E-mail: [email protected] for more papers by this author First published: 09 August 2013 https://doi.org/10.1096/fj.13-236851Citations: 24 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Pin1, a conserved eukaryotic peptidyl-prolyl cis/trans isomerase, has profound effects on numerous key-signaling molecules, and its deregulation contributes to disease, particularly cancer. Although Pin1-mediated prolyl isomerization of protein servers as a regulatory switch in signaling pathways, the significance of proline isomerase activity in chromatin modifying complex remains unclear. Here, we identify Pin1 as a key negative regulator for suppressor of variegation 3–9 homologue 1 (SUV39H1) stability, a major methyltransferase responsible for histone H3 trimethylation on Lys9 (H3K9me3). Pin1 interacts with SUV39H1 in a phosphorylation-dependent manner and promotes ubiquitination-mediated degradation of SUV39H1. Consequently, Pin1 reduces SUV39H1 abundance and suppresses SUV39H1 ability to induce H3K9me3. In contrast, depletion of Pin1 in cancer cells leads to elevated SUV39H1 expression, which subsequently increases H3K9me3, inhibiting tumorigenecity of cancer cells. In a xenograft model with 4T1 metastatic mouse breast carcinoma cells, Pin1 overexpression increases tumor growth, whereas SUV39H1 overexpression abrogates it. In human breast cancer patients, immunohistochemical staining shows that Pin1 levels are negatively correlated with SUV39H1 as well as H3K9me3 levels. Thus, Pin1-mediated reduction of SUV39H1 stability contributes to convey oncogenic signals for aggressiveness of human breast cancer, suggesting that Pin1 may be a promising drug target for anticancer therapy.—Khanal, P., Kim, G., Lim, S.-C, Yun, H.-J., Lee, K. Y., Choi, H.-K., Choi, H. S. Prolyl isomerase Pin1 negatively regulates the stability of SUV39H1 to promote tumorigenesis in breast cancer. FASEB J. 27, 4606–4618 (2013). www.fasebj.org Citing Literature Volume27, Issue11November 2013Pages 4606-4618 RelatedInformation