CENPF

{{short description|Centromere- and microtubule-associated protein}}

{{Infobox_gene}}

Centromere protein F is a protein that in humans is encoded by the CENPF gene.{{cite journal|vauthors=Rattner JB, Rao A, Fritzler MJ, Valencia DW, Yen TJ|date=Mar 1994|title=CENP-F is a .ca 400 kDa kinetochore protein that exhibits a cell-cycle dependent localization|journal=Cell Motil Cytoskeleton|volume=26|issue=3|pages=214–26|doi=10.1002/cm.970260305|pmid=7904902}}{{cite journal|vauthors=Testa JR, Zhou JY, Bell DW, Yen TJ|date=Mar 1995|title=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|journal=Genomics|volume=23|issue=3|pages=691–3|doi=10.1006/geno.1994.1558|pmid=7851898}}{{cite web | title = Entrez Gene: CENPF centromere protein F, 350/400ka (mitosin)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1063}} It is involved in chromosome segregation during cell division. It also has a role in the orientation of microtubules to form cellular cilia.{{Cite journal|last1=Waters|first1=Aoife M.|last2=Asfahani|first2=Rowan|last3=Carroll|first3=Paula|last4=Bicknell|first4=Louise|last5=Lescai|first5=Francesco|last6=Bright|first6=Alison|last7=Chanudet|first7=Estelle|last8=Brooks|first8=Anthony|last9=Christou-Savina|first9=Sonja|last10=Osman|first10=Guled|last11=Walsh|first11=Patrick|date=March 2015|title=The kinetochore protein, CENPF, is mutated in human ciliopathy and microcephaly phenotypes|journal=Journal of Medical Genetics|volume=52|issue=3|pages=147–156|doi=10.1136/jmedgenet-2014-102691|issn=1468-6244|pmc=4345935|pmid=25564561}}{{Cite journal|last1=Filges|first1=Isabel|last2=Bruder|first2=Elisabeth|last3=Brandal|first3=Kristin|last4=Meier|first4=Stephanie|last5=Undlien|first5=Dag Erik|last6=Waage|first6=Trine Rygvold|last7=Hoesli|first7=Irene|last8=Schubach|first8=Max|last9=de Beer|first9=Tjaart|last10=Sheng|first10=Ying|last11=Hoeller|first11=Sylvia|date=April 2016|title=Strømme Syndrome Is a Ciliary Disorder Caused by Mutations in CENPF|journal=Human Mutation|volume=37|issue=4|pages=359–363|doi=10.1002/humu.22960|issn=1098-1004|pmid=26820108|s2cid=1495539|doi-access=free}}

Function

CENPF 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.

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.{{Cite web|url=https://www.omim.org/entry/243605|title=OMIM Entry - # 243605 - STROMME SYNDROME; STROMS|website=www.omim.org|language=en-us|access-date=2018-09-27}}

CENPF is thought to form either a homodimer or heterodimer.

Clinical significance

Mutations in both copies of CENPF cause Strømme syndrome, characterised by microcephaly, eye abnormalities and apple-peel jejunal atresia.{{Cite journal|last1=Filges|first1=Isabel|last2=Bruder|first2=Elisabeth|last3=Brandal|first3=Kristin|last4=Meier|first4=Stephanie|last5=Undlien|first5=Dag Erik|last6=Waage|first6=Trine Rygvold|last7=Hoesli|first7=Irene|last8=Schubach|first8=Max|last9=de Beer|first9=Tjaart|last10=Sheng|first10=Ying|last11=Hoeller|first11=Sylvia|date=April 2016|title=Strømme Syndrome Is a Ciliary Disorder Caused by Mutations in CENPF|journal=Human Mutation|volume=37|issue=4|pages=359–363|doi=10.1002/humu.22960|issn=1098-1004|pmid=26820108|s2cid=1495539|doi-access=free}} Autoantibodies against CENPF have been found in patients with cancer or graft-versus-host disease.

See also

References

{{reflist}}

Further reading

{{refbegin | 2}}

  • {{cite journal | vauthors=Ma L, Zhao X, Zhu X |title=Mitosin/CENP-F in mitosis, transcriptional control, and differentiation. |journal=J. Biomed. Sci. |volume=13 |issue= 2 |pages= 205–13 |year= 2006 |pmid= 16456711 |doi= 10.1007/s11373-005-9057-3 |doi-access= free }}
  • {{cite journal | vauthors=Liao H, Winkfein RJ, Mack G |title=CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis. |journal=J. Cell Biol. |volume=130 |issue= 3 |pages= 507–18 |year= 1995 |pmid= 7542657 |doi=10.1083/jcb.130.3.507 | pmc=2120529 |display-authors=etal}}
  • {{cite journal | vauthors=Li Q, Ke Y, Kapp JA |title=A novel cell-cycle-dependent 350-kDa nuclear protein: C-terminal domain sufficient for nuclear localization. |journal=Biochem. Biophys. Res. Commun. |volume=212 |issue= 1 |pages= 220–8 |year= 1995 |pmid= 7612011 |doi=10.1006/bbrc.1995.1959 |display-authors=etal}}
  • {{cite journal | vauthors=Zhu X, Chang KH, He D |title=The C terminus of mitosin is essential for its nuclear localization, centromere/kinetochore targeting, and dimerization. |journal=J. Biol. Chem. |volume=270 |issue= 33 |pages= 19545–50 |year= 1995 |pmid= 7642639 |doi=10.1074/jbc.270.33.19545 |display-authors=etal|doi-access=free }}
  • {{cite journal | vauthors=Zhu X, Mancini MA, Chang KH |title=Characterization of a novel 350-kilodalton nuclear phosphoprotein that is specifically involved in mitotic-phase progression. |journal=Mol. Cell. Biol. |volume=15 |issue= 9 |pages= 5017–29 |year= 1995 |pmid= 7651420 |doi= 10.1128/MCB.15.9.5017| pmc=230749 |display-authors=etal}}
  • {{cite journal | vauthors=Li S, Ku CY, Farmer AA |title=Identification of a novel cytoplasmic protein that specifically binds to nuclear localization signal motifs. |journal=J. Biol. Chem. |volume=273 |issue= 11 |pages= 6183–9 |year= 1998 |pmid= 9497340 |doi=10.1074/jbc.273.11.6183 |display-authors=etal|doi-access=free }}
  • {{cite journal | vauthors=Chan GK, Schaar BT, Yen TJ |title=Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1. |journal=J. Cell Biol. |volume=143 |issue= 1 |pages= 49–63 |year= 1998 |pmid= 9763420 |doi=10.1083/jcb.143.1.49 | pmc=2132809 }}
  • {{cite journal | author=Zhu X |title=Structural requirements and dynamics of mitosin-kinetochore interaction in M phase. |journal=Mol. Cell. Biol. |volume=19 |issue= 2 |pages= 1016–24 |year= 1999 |pmid= 9891037 |doi= 10.1128/MCB.19.2.1016| pmc=116032 }}
  • {{cite journal | vauthors=Erlanson M, Casiano CA, Tan EM |title=Immunohistochemical analysis of the proliferation associated nuclear antigen CENP-F in non-Hodgkin's lymphoma. |journal=Mod. Pathol. |volume=12 |issue= 1 |pages= 69–74 |year= 1999 |pmid= 9950165 |display-authors=etal}}
  • {{cite journal | vauthors=Goodwin RL, Pabón-Peña LM, Foster GC, Bader D |title=The cloning and analysis of LEK1 identifies variations in the LEK/centromere protein F/mitosin gene family. |journal=J. Biol. Chem. |volume=274 |issue= 26 |pages= 18597–604 |year= 1999 |pmid= 10373470 |doi=10.1074/jbc.274.26.18597 |doi-access=free }}
  • {{cite journal | vauthors=Ashar HR, James L, Gray K |title=Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules. |journal=J. Biol. Chem. |volume=275 |issue= 39 |pages= 30451–7 |year= 2000 |pmid= 10852915 |doi= 10.1074/jbc.M003469200 |display-authors=etal|doi-access=free }}
  • {{cite journal | vauthors=Kobayashi M, Hanai R |title=M phase-specific association of human topoisomerase IIIbeta with chromosomes. |journal=Biochem. Biophys. Res. Commun. |volume=287 |issue= 1 |pages= 282–7 |year= 2001 |pmid= 11549288 |doi= 10.1006/bbrc.2001.5580 }}
  • {{cite journal | vauthors=Hussein D, Taylor SS |title=Farnesylation of Cenp-F is required for G2/M progression and degradation after mitosis. |journal=J. Cell Sci. |volume=115 |issue= Pt 17 |pages= 3403–14 |year= 2003 |doi=10.1242/jcs.115.17.3403 |pmid= 12154071 |doi-access=free }}
  • {{cite journal | vauthors=Holstein SA, Hohl RJ |title=Synergistic interaction of lovastatin and paclitaxel in human cancer cells. |journal=Mol. Cancer Ther. |volume=1 |issue= 2 |pages= 141–9 |year= 2003 |pmid= 12467231 }}
  • {{cite journal | vauthors=Konstantinidou AE, Korkolopoulou P, Kavantzas N |title=Mitosin, a novel marker of cell proliferation and early recurrence in intracranial meningiomas. |journal=Histol. Histopathol. |volume=18 |issue= 1 |pages= 67–74 |year= 2003 |pmid= 12507285 |display-authors=etal}}
  • {{cite journal | vauthors=Yang ZY, Guo J, Li N |title=Mitosin/CENP-F is a conserved kinetochore protein subjected to cytoplasmic dynein-mediated poleward transport. |journal=Cell Res. |volume=13 |issue= 4 |pages= 275–83 |year= 2004 |pmid= 12974617 |doi= 10.1038/sj.cr.7290172 |display-authors=etal|doi-access=free }}
  • {{cite journal | vauthors=Laoukili J, Kooistra MR, Brás A |title=FoxM1 is required for execution of the mitotic programme and chromosome stability. |journal=Nat. Cell Biol. |volume=7 |issue= 2 |pages= 126–36 |year= 2005 |pmid= 15654331 |doi= 10.1038/ncb1217 |s2cid=11732068 |display-authors=etal}}
  • {{cite journal | vauthors=Zhou X, Wang R, Fan L |title=Mitosin/CENP-F as a negative regulator of activating transcription factor-4. |journal=J. Biol. Chem. |volume=280 |issue= 14 |pages= 13973–7 |year= 2005 |pmid= 15677469 |doi= 10.1074/jbc.M414310200 |display-authors=etal|doi-access=free }}

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{{Chromosome genetics}}