Mammalian CBX7 isoforms p36 and p22 exhibit differential responses to serum, varying functions for proliferation, and distinct subcellular localization

• Type of Material: Article
• Authors: Kyu-Won Cho, Emory University; Mark Andrade, Emory University; Yu Zhang, Emory University; Young Yoon, Emory University
• Language: English
• Date: 2020-05-15
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-020-64908-2
• Title of Journal or Parent Work: Scientific Reports
• Volume: 10
• Issue: 1
• Start Page: 8061
• End Page: 8061
• Grant/Funding Information: This work was supported by grants from NHLBI (R01HL127759, R01HL129511) and NIDDK (DP3-DK108245), and the grants from the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIP) (No 2015M3A9C6031514), and Faculty Research Assistance Program of Yonsei University College of Medicine 2018 (6-2018-0114).; K. C. is a recipient of an American Heart Association predoctoral fellowship grant (16PRE31350034).
• Keywords: Polycomb-Group Proteins; Cancer; Phosphorylation; Science & Technology; Epigenetic regulation; Multidisciplinary Sciences; Epigenomics; Methylation; Genes; Science & Technology - Other Topics; Opposing roles; Regulates cell-proliferation; Histone H3
• Research Categories: Biology, Genetics; Engineering, Biomedical; Biology, Cell

Abstract

CBX7 is a polycomb group protein, and despite being implicated in many diseases, its role in cell proliferation has been controversial: some groups described its pro-proliferative properties, but others illustrated its inhibitory effects on cell growth. To date, the reason for the divergent observations remains unknown. While several isoforms for CBX7 were reported, no studies investigated whether the divergent roles of CBX7 could be due to distinct functions of CBX7 isoforms. In this study, we newly identified mouse CBX7 transcript variant 1 (mCbx7v1), which is homologous to the human CBX7 gene (hCBX7v1) and is expressed in various mouse organs. We revealed that mCbx7v1 and hCBX7v1 encode a 36 kDa protein (p36CBX7) whereas mCbx7 and hCBX7v3 encode a 22 kDa protein (p22CBX7). This study further demonstrated that p36CBX7 was localized to the nucleus and endogenously expressed in proliferating cells whereas p22CBX7 was localized to the cytoplasm, induced by serum starvation in both human and mouse cells, and inhibited cell proliferation. Together, these data indicate that CBX7 isoforms are localized in different locations in a cell and play differing roles in cell proliferation. This varying function of CBX7 isoforms may help us understand the distinct function of CBX7 in various studies.