{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:47:44Z","timestamp":1789616864391,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zhejiang Provincial Public Welfare Technology Application Research Project","award":["LGN21C010001"],"award-info":[{"award-number":["LGN21C010001"]}]},{"name":"Zhejiang Provincial Public Welfare Technology Application Research Project","award":["2024JJ4053"],"award-info":[{"award-number":["2024JJ4053"]}]},{"name":"Hunan Provincial Natural Science Foundation of China","award":["LGN21C010001"],"award-info":[{"award-number":["LGN21C010001"]}]},{"name":"Hunan Provincial Natural Science Foundation of China","award":["2024JJ4053"],"award-info":[{"award-number":["2024JJ4053"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Ulp1 is a vital regulator of the cell cycle, with its absence leading to G2\/M phase arrest in Saccharomyces cerevisiae. This study aims to investigate the role of Ulp1 in cell cycle regulation in Pichia pastoris and to elucidate its mechanisms of action, particularly through the modulation of the gene INO1. Methods: We generated Ulp1 knockout strains in Pichia pastoris using the FLP-FRT system and performed RNA sequencing (RNA-seq) to analyze gene expression changes. We assessed cell proliferation in Ulp1 knockout and INO1 overexpressing strains, as well as the effects of inositol supplementation. Results: Our findings revealed significant downregulation of INO1 and other genes in Ulp1 knockout strains. Importantly, overexpression of INO1 restored cell proliferation, indicating that Ulp1 regulates this process via INO1. Notably, supplementation with exogenous inositol did not rescue cell proliferation, suggesting that the enzymatic activity of INO1 is not required for Ulp1\u2019s regulatory function. Conclusions: This study demonstrates that Ulp1 modulates cell proliferation in Pichia pastoris through INO1, independent of its enzymatic activity. These insights enhance our understanding of Ulp1\u2019s role in cell cycle regulation and open new avenues for exploring the molecular mechanisms governing yeast cell division. Further investigations are warranted to delineate the intricate regulatory pathways involved in this process.<\/jats:p>","DOI":"10.3390\/genes15111459","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T06:10:48Z","timestamp":1731478248000},"page":"1459","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ulp1 Regulates Cell Proliferation Through INO1 in Pichia pastoris"],"prefix":"10.3390","volume":"15","author":[{"given":"Junjie","family":"Yang","sequence":"first","affiliation":[{"name":"College of Life Sciences and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2585-3547","authenticated-orcid":false,"given":"Bo","family":"Zhong","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Jia","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixi","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0554-7853","authenticated-orcid":false,"given":"Wenjie","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenna","family":"Shang","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6691-9816","authenticated-orcid":false,"given":"Xiaofeng","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengbing","family":"Lyu","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou 310018, China"},{"name":"Zhejiang Sci-Tech University Shaoxing Academy of Biomedicine Co., Ltd., Shaoxing 312369, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qijing","family":"Gai","sequence":"additional","affiliation":[{"name":"Zhejiang Q-Peptide Biotechnology Co., Ltd., Shaoxing 312366, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6793-164X","authenticated-orcid":false,"given":"Jianqing","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou 310018, China"},{"name":"Zhejiang Sci-Tech University Shaoxing Academy of Biomedicine Co., Ltd., Shaoxing 312369, China"},{"name":"Zhejiang Q-Peptide Biotechnology Co., Ltd., Shaoxing 312366, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9399-9252","authenticated-orcid":false,"given":"Guodong","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Central South University, Changsha 410031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"key":"ref_1","unstructured":"Kroetz, M.B. 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