{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T01:16:38Z","timestamp":1784078198677,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,4,3]],"date-time":"2016-04-03T00:00:00Z","timestamp":1459641600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81270887"],"award-info":[{"award-number":["81270887"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81270495"],"award-info":[{"award-number":["81270495"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["30801218"],"award-info":[{"award-number":["30801218"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Protein phosphatase 4 (<jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>4) has been reported to be indispensable for cell proliferation and survival. Deletion of <jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>4 has been shown to induce abnormal and even lethal events in growth and development both in lower eukaryotes and in mammals. However, until now, effects of <jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>4 up\u2010regulation have remained unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>To test effects of <jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>4 on cell proliferation, cell cycle and morphology in HepG2 cells, it was down\u2010regulated using <jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>4 si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> or its activity was inhibited using <jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>4<jats:styled-content style=\"fixed-case\">RL<\/jats:styled-content> (a <jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>4 phosphatase\u2010dead mutant) adenoviruses. Alternatively, <jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>4 was up\u2010regulated using <jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>4 adenoviruses. Next, we used a functional proteomic approach to identify proteins that may interact with <jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>4. Furthermore, we performed rescue experiments to verify the possible mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>To our surprise, we found that both up\u2010regulation and inhibition of <jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>4 inhibited cell proliferation. Unlike <jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>4 inhibition, <jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>4 up\u2010regulation induced prominent arrest at the prometaphase\/metaphase transition by causing defects in chromosome alignment and spindle assembly. Moreover, we identified scaffold attachment factor A (<jats:styled-content style=\"fixed-case\">SAF<\/jats:styled-content>\u2010A) (an important protein required for kinetochore\u2010microtubule attachment that participates in the prometaphase\/metaphase transition), to be a novel protein that interacts with <jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>4, using a proteomic approach. Thus, mutual regulatory mechanisms exist between <jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>4 and <jats:styled-content style=\"fixed-case\">SAF<\/jats:styled-content>\u2010A. Interactions between <jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>4 and <jats:styled-content style=\"fixed-case\">SAF<\/jats:styled-content>\u2010A played a role in prometaphase\/metaphase transition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data demonstrate a novel regulatory mechanism involving <jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>4 in cell proliferation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cpr.12249","type":"journal-article","created":{"date-parts":[[2016,4,4]],"date-time":"2016-04-04T04:13:02Z","timestamp":1459743182000},"page":"219-235","source":"Crossref","is-referenced-by-count":14,"title":["Protein phosphatase 4 plays dual roles during cell proliferation"],"prefix":"10.1111","volume":"49","author":[{"given":"Xiuqing","family":"Huang","sequence":"first","affiliation":[{"name":"The Key Laboratory of Geriatrics Beijing Hospital &amp; Beijing Institute of Geriatrics Ministry of Health Beijing 100730 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Sciences Beijing Normal University Beijing 100875 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Shen","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Geriatrics Beijing Hospital &amp; 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