Centromere protein F is a protein that in humans is encoded by the CENPF gene.[5][6][7] It is involved in chromosome segregation during cell division. It also has a role in the orientation of microtubules to form cellular cilia.[8][9]
Function
editCENPF is part of the nuclear matrix during the G2 phase of the cell cycle (the phase of rapid protein synthesis in preparation for mitosis). In late G2, the protein forms part of the kinetochore, a disc-shaped protein complex that allows the centromere of two sister chromatids to attach to microtubules (forming the spindle apparatus) in order for the microtubules to pull them apart in the process of dividing the cell. It remains part of the kinetochore through early anaphase (the chromosome-dividing phase). In late anaphase, CENPF localises to the spindle midzone, and in telophase (the cell-dividing phase) it localises to the intercellular bridge. It is thought to be subsequently degraded. Mutations in CENPF lead to impaired cell division during early development. Mitosis has been found to take longer when the gene is mutated.[8][9]
Microtubules are protein structures that are part of the cytoskeleton and are necessary for cells to have diverse, complex shapes and migratory ability. They are made by the centrosome, which contains a pair of cylindrical centrioles at right-angles to each other. Before division, CENPF localises at the end of one of the centrioles (the mother centriole) in order to orient microtubules correctly to form thin cellular projections called cilia. Most cilia are primary cilia, which are involved in cell signalling to trigger migration, division or differentiation. Mutations in CENPF disrupt this ability to form cilia; cilia have been found to be fewer in number and shorter when the gene is mutated.[8][10]
CENPF is thought to form either a homodimer or heterodimer.
Clinical significance
editMutations in both copies of CENPF cause Strømme syndrome, characterised by microcephaly, eye abnormalities and apple-peel jejunal atresia.[11] Autoantibodies against CENPF have been found in patients with cancer or graft-versus-host disease.[7]
See also
editReferences
edit- ^ a b c GRCh38: Ensembl release 89: ENSG00000117724 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026605 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Rattner JB, Rao A, Fritzler MJ, Valencia DW, Yen TJ (Mar 1994). "CENP-F is a .ca 400 kDa kinetochore protein that exhibits a cell-cycle dependent localization". Cell Motil Cytoskeleton. 26 (3): 214–26. doi:10.1002/cm.970260305. PMID 7904902.
- ^ Testa JR, Zhou JY, Bell DW, Yen TJ (Mar 1995). "Chromosomal localization of the genes encoding the kinetochore proteins CENPE and CENPF to human chromosomes 4q24→q25 and 1q32→q41, respectively, by fluorescence in situ hybridization". Genomics. 23 (3): 691–3. doi:10.1006/geno.1994.1558. PMID 7851898.
- ^ a b "Entrez Gene: CENPF centromere protein F, 350/400ka (mitosin)".
- ^ a b c Waters, Aoife M.; Asfahani, Rowan; Carroll, Paula; Bicknell, Louise; Lescai, Francesco; Bright, Alison; Chanudet, Estelle; Brooks, Anthony; Christou-Savina, Sonja; Osman, Guled; Walsh, Patrick (March 2015). "The kinetochore protein, CENPF, is mutated in human ciliopathy and microcephaly phenotypes". Journal of Medical Genetics. 52 (3): 147–156. doi:10.1136/jmedgenet-2014-102691. ISSN 1468-6244. PMC 4345935. PMID 25564561.
- ^ a b Filges, Isabel; Bruder, Elisabeth; Brandal, Kristin; Meier, Stephanie; Undlien, Dag Erik; Waage, Trine Rygvold; Hoesli, Irene; Schubach, Max; de Beer, Tjaart; Sheng, Ying; Hoeller, Sylvia (April 2016). "Strømme Syndrome Is a Ciliary Disorder Caused by Mutations in CENPF". Human Mutation. 37 (4): 359–363. doi:10.1002/humu.22960. ISSN 1098-1004. PMID 26820108. S2CID 1495539.
- ^ "OMIM Entry - # 243605 - STROMME SYNDROME; STROMS". www.omim.org. Retrieved 2018-09-27.
- ^ Filges, Isabel; Bruder, Elisabeth; Brandal, Kristin; Meier, Stephanie; Undlien, Dag Erik; Waage, Trine Rygvold; Hoesli, Irene; Schubach, Max; de Beer, Tjaart; Sheng, Ying; Hoeller, Sylvia (April 2016). "Strømme Syndrome Is a Ciliary Disorder Caused by Mutations in CENPF". Human Mutation. 37 (4): 359–363. doi:10.1002/humu.22960. ISSN 1098-1004. PMID 26820108. S2CID 1495539.
External links
edit- Human CENPF genome location and CENPF gene details page in the UCSC Genome Browser.
Further reading
edit- Ma L, Zhao X, Zhu X (2006). "Mitosin/CENP-F in mitosis, transcriptional control, and differentiation". J. Biomed. Sci. 13 (2): 205–13. doi:10.1007/s11373-005-9057-3. PMID 16456711.
- Liao H, Winkfein RJ, Mack G, et al. (1995). "CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis". J. Cell Biol. 130 (3): 507–18. doi:10.1083/jcb.130.3.507. PMC 2120529. PMID 7542657.
- Li Q, Ke Y, Kapp JA, et al. (1995). "A novel cell-cycle-dependent 350-kDa nuclear protein: C-terminal domain sufficient for nuclear localization". Biochem. Biophys. Res. Commun. 212 (1): 220–8. doi:10.1006/bbrc.1995.1959. PMID 7612011.
- Zhu X, Chang KH, He D, et al. (1995). "The C terminus of mitosin is essential for its nuclear localization, centromere/kinetochore targeting, and dimerization". J. Biol. Chem. 270 (33): 19545–50. doi:10.1074/jbc.270.33.19545. PMID 7642639.
- Zhu X, Mancini MA, Chang KH, et al. (1995). "Characterization of a novel 350-kilodalton nuclear phosphoprotein that is specifically involved in mitotic-phase progression". Mol. Cell. Biol. 15 (9): 5017–29. doi:10.1128/MCB.15.9.5017. PMC 230749. PMID 7651420.
- Li S, Ku CY, Farmer AA, et al. (1998). "Identification of a novel cytoplasmic protein that specifically binds to nuclear localization signal motifs". J. Biol. Chem. 273 (11): 6183–9. doi:10.1074/jbc.273.11.6183. PMID 9497340.
- Chan GK, Schaar BT, Yen TJ (1998). "Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1". J. Cell Biol. 143 (1): 49–63. doi:10.1083/jcb.143.1.49. PMC 2132809. PMID 9763420.
- Zhu X (1999). "Structural requirements and dynamics of mitosin-kinetochore interaction in M phase". Mol. Cell. Biol. 19 (2): 1016–24. doi:10.1128/MCB.19.2.1016. PMC 116032. PMID 9891037.
- Erlanson M, Casiano CA, Tan EM, et al. (1999). "Immunohistochemical analysis of the proliferation associated nuclear antigen CENP-F in non-Hodgkin's lymphoma". Mod. Pathol. 12 (1): 69–74. PMID 9950165.
- Goodwin RL, Pabón-Peña LM, Foster GC, Bader D (1999). "The cloning and analysis of LEK1 identifies variations in the LEK/centromere protein F/mitosin gene family". J. Biol. Chem. 274 (26): 18597–604. doi:10.1074/jbc.274.26.18597. PMID 10373470.
- Ashar HR, James L, Gray K, et al. (2000). "Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules". J. Biol. Chem. 275 (39): 30451–7. doi:10.1074/jbc.M003469200. PMID 10852915.
- Kobayashi M, Hanai R (2001). "M phase-specific association of human topoisomerase IIIbeta with chromosomes". Biochem. Biophys. Res. Commun. 287 (1): 282–7. doi:10.1006/bbrc.2001.5580. PMID 11549288.
- Hussein D, Taylor SS (2003). "Farnesylation of Cenp-F is required for G2/M progression and degradation after mitosis". J. Cell Sci. 115 (Pt 17): 3403–14. doi:10.1242/jcs.115.17.3403. PMID 12154071.
- Holstein SA, Hohl RJ (2003). "Synergistic interaction of lovastatin and paclitaxel in human cancer cells". Mol. Cancer Ther. 1 (2): 141–9. PMID 12467231.
- Konstantinidou AE, Korkolopoulou P, Kavantzas N, et al. (2003). "Mitosin, a novel marker of cell proliferation and early recurrence in intracranial meningiomas". Histol. Histopathol. 18 (1): 67–74. PMID 12507285.
- Yang ZY, Guo J, Li N, et al. (2004). "Mitosin/CENP-F is a conserved kinetochore protein subjected to cytoplasmic dynein-mediated poleward transport". Cell Res. 13 (4): 275–83. doi:10.1038/sj.cr.7290172. PMID 12974617.
- Laoukili J, Kooistra MR, Brás A, et al. (2005). "FoxM1 is required for execution of the mitotic programme and chromosome stability". Nat. Cell Biol. 7 (2): 126–36. doi:10.1038/ncb1217. PMID 15654331. S2CID 11732068.
- Zhou X, Wang R, Fan L, et al. (2005). "Mitosin/CENP-F as a negative regulator of activating transcription factor-4". J. Biol. Chem. 280 (14): 13973–7. doi:10.1074/jbc.M414310200. PMID 15677469.