PMID- 31208979 OWN - NLM STAT- MEDLINE DCOM- 20200127 LR - 20200309 IS - 1098-5549 (Electronic) IS - 0270-7306 (Print) IS - 0270-7306 (Linking) VI - 39 IP - 17 DP - 2019 Sep 1 TI - Comprehensive Analysis of Mouse Cancer/Testis Antigen Functions in Cancer Cells and Roles of TEKT5 in Cancer Cells and Testicular Germ Cells. LID - 10.1128/MCB.00154-19 [doi] LID - e00154-19 AB - The cancer/testis antigen (CTA) genes were identified as human genes preferentially expressed in cancer cells and testis, but the contribution of CTAs to cancer and male germ cell development is unclear. In this study, we comprehensively examined mouse CTA functions and found that the majority of CTAs are involved in growth and/or survival of cancer cells. We focused on one mouse CTA gene, Tekt5, for its detailed functional analysis. Tekt5 knockdown (KD) in ovarian cancer cells caused G(1) arrest and apoptosis, and p27(kip1) was concomitantly upregulated. Tekt5 KD also resulted in decreased levels of acetylated alpha-tubulin and subsequent fragmentation of beta-III-tubulin, upregulation of HDAC6 that deacetylates alpha-tubulin, and nuclear accumulation of SMAD3 that induces p27(kip1) expression. Because depolymerization of tubulin is known to cause translocation of SMAD3 to the nucleus, these results together suggested that TEKT5 negatively regulates Hdac6 expression and consequently maintains cell cycle via stabilization of tubulin. We also found that the number of spermatids was significantly decreased and acetylated alpha-tubulin levels were decreased in vivo by KD of Tekt5 in testis. Because acetylated alpha-tubulin is required for sperm morphogenesis, these results suggest that TEKT5 is necessary for spermiogenesis via maintenance of acetylated alpha-tubulin levels. CI - Copyright (c) 2019 American Society for Microbiology. FAU - Aoki, Nana AU - Aoki N AD - Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan. AD - Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi, Japan. FAU - Matsui, Yasuhisa AU - Matsui Y AUID- ORCID: 0000-0001-7026-6355 AD - Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan yasuhisa.matsui.d3@tohoku.ac.jp. AD - Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi, Japan. AD - Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan. AD - The Japan Agency for Medical Research and Development-Core Research for Evolutional Science and Technology (AMED-CREST), Tokyo, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190812 PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (Cdkn1b protein, mouse) RN - 0 (Microtubule Proteins) RN - 0 (Smad3 Protein) RN - 0 (Smad3 protein, mouse) RN - 0 (Tubulin) RN - 0 (tektins) RN - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27) RN - EC 3.5.1.98 (Hdac6 protein, mouse) RN - EC 3.5.1.98 (Histone Deacetylase 6) SB - IM MH - Acetylation MH - Animals MH - Cell Differentiation MH - Cell Line, Tumor MH - Cell Proliferation MH - Cell Survival MH - Cyclin-Dependent Kinase Inhibitor p27/genetics MH - Female MH - Gene Expression Regulation, Neoplastic MH - Histone Deacetylase 6/metabolism MH - Male MH - Mice MH - Microtubule Proteins/*genetics MH - Ovarian Neoplasms/*genetics MH - Protein Stability MH - Smad3 Protein/metabolism MH - *Spermatogenesis MH - Spermatozoa/*cytology/metabolism MH - Tubulin/chemistry/*metabolism PMC - PMC6692122 OTO - NOTNLM OT - CTA OT - Tekt5 OT - cancer cell OT - germ cell EDAT- 2019/06/19 06:00 MHDA- 2020/01/28 06:00 PMCR- 2020/02/12 CRDT- 2019/06/19 06:00 PHST- 2019/04/10 00:00 [received] PHST- 2019/06/06 00:00 [accepted] PHST- 2019/06/19 06:00 [pubmed] PHST- 2020/01/28 06:00 [medline] PHST- 2019/06/19 06:00 [entrez] PHST- 2020/02/12 00:00 [pmc-release] AID - MCB.00154-19 [pii] AID - 00154-19 [pii] AID - 10.1128/MCB.00154-19 [doi] PST - epublish SO - Mol Cell Biol. 2019 Aug 12;39(17):e00154-19. doi: 10.1128/MCB.00154-19. Print 2019 Sep 1.