{"doi":"10.1091/mbc.e09-07-0560","title":"Murine CENP-F Regulates Centrosomal Microtubule Nucleation and Interacts with Hook2 at the Centrosome","abstract":"<jats:p>The microtubule (MT) network is essential in a broad spectrum of cellular functions. Many studies have linked CENP-F to MT-based activities as disruption of this protein leads to major changes in MT structure and function. Still, the basis of CENP-F regulation of the MT network remains elusive. Here, our studies reveal a novel and critical localization and role for CENP-F at the centrosome, the major MT organizing center (MTOC) of the cell. Using a yeast two-hybrid screen, we identify Hook2, a linker protein that is essential for regulation of the MT network at the centrosome, as a binding partner of CENP-F. With recently developed immunochemical reagents, we confirm this interaction and reveal the novel localization of CENP-F at the centrosome. Importantly, in this first report of CENP-F<jats:sup>−/−</jats:sup>cells, we demonstrate that ablation of CENP-F protein function eliminates MT repolymerization after standard nocodazole treatment. This inhibition of MT regrowth is centrosome specific because MT repolymerization is readily observed from the Golgi in CENP-F<jats:sup>−/−</jats:sup>cells. The centrosome-specific function of CENP-F in the regulation of MT growth is confirmed by expression of truncated CENP-F containing only the Hook2-binding domain. Furthermore, analysis of partially reconstituted MTOC asters in cells that escape complete repolymerization block shows that disruption of CENP-F function impacts MT nucleation and anchoring rather than promoting catastrophe. Our study reveals a major new localization and function of CENP-F at the centrosome that is likely to impact a broad array of MT-based actions in the cell.</jats:p>","journal":"Molecular Biology of the Cell","year":2009,"id":596865,"datarank":0.5416376868966337,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"self_citation_contribution":0.5416376868966337,"citation_network_contribution":0.0,"self_endowment_contribution":0.5416376868966337,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1528793,"name":"Ryan Pooley","orcid":null,"position":1,"is_corresponding":false},{"id":1528794,"name":"Paul M. 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Here, our studies reveal a novel and critical localization and role for CENP-F at the centrosome, the major MT organizing center (MTOC) of the cell. Using a yeast two-hybrid screen, we identify Hook2, a linker protein that is essential for regulation of the MT network at the centrosome, as a binding partner of CENP-F. With recently developed immunochemical reagents, we confirm this interaction and reveal the novel localization of CENP-F at the centrosome. Importantly, in this first report of CENP-F<jats:sup>−/−</jats:sup>cells, we demonstrate that ablation of CENP-F protein function eliminates MT repolymerization after standard nocodazole treatment. This inhibition of MT regrowth is centrosome specific because MT repolymerization is readily observed from the Golgi in CENP-F<jats:sup>−/−</jats:sup>cells. The centrosome-specific function of CENP-F in the regulation of MT growth is confirmed by expression of truncated CENP-F containing only the Hook2-binding domain. Furthermore, analysis of partially reconstituted MTOC asters in cells that escape complete repolymerization block shows that disruption of CENP-F function impacts MT nucleation and anchoring rather than promoting catastrophe. Our study reveals a major new localization and function of CENP-F at the centrosome that is likely to impact a broad array of MT-based actions in the cell.</jats:p>","is_dataset_classified":null,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19793914","pmcid":"PMC2777108","openalex_id":"https://openalex.org/W2099804406","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"DK-59637","title":null},{"funder_name":"NEI NIH HHS","grant_id":"EY08126","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA068485","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK020593","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK058404","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL-037675","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA-68485","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"1R01 GM-078373-01","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK-20593","title":null},{"funder_name":"NEI NIH HHS","grant_id":"P30 EY008126","title":null},{"funder_name":"NICHD NIH HHS","grant_id":"P30 HD015052","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P60 DK020593","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"5 T32HL07751","title":null},{"funder_name":"NICHD NIH HHS","grant_id":"HD-15052","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM078373","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL037675","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"T32 HL007751","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK-58404","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"U24 DK059637","title":null}],"total_grants":19,"fwci":0.7614,"citation_percentile":0.69643411,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":2},{"year":2014,"count":4},{"year":2015,"count":5},{"year":2016,"count":6},{"year":2017,"count":1},{"year":2018,"count":6},{"year":2019,"count":4},{"year":2023,"count":2}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2777108","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2777108","host_type":"repository"},{"url":"https://doi.org/10.1091/mbc.e09-07-0560","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19793914","host_type":"repository"}],"fields_of_study":["Microtubule and mitosis dynamics","Plant Molecular Biology Research","Genomics and Chromatin Dynamics","Animals","COS Cells","Cell Line","Centrosome","Chlorocebus aethiops","Chromosomal Proteins, Non-Histone","Humans","Mice","Mice, Knockout","Microfilament Proteins","Microtubule-Associated Proteins","Microtubule-Organizing Center","Microtubules","Nocodazole","Tubulin Modulators","Two-Hybrid System Techniques"],"mesh_terms":["Animals","Cell Line","Chlorocebus aethiops","Chromosomal Proteins, Non-Histone","Humans","Microfilament Proteins","Microtubule-Associated Proteins","Microtubules","Nocodazole","Mice, Knockout","Centrosome","COS Cells","Two-Hybrid System Techniques","Microtubule-Organizing Center","Tubulin Modulators","Mice"],"keywords":["Centrosome","Microtubule organizing center","Biology","Cell biology","Microtubule nucleation","Centrosome cycle","Microtubule","Nocodazole","Spindle pole body","Cell division","Cell cycle","Cell","Genetics","Spindle apparatus","Cytoskeleton"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T11:33:17.279406Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}