PRC1

For polycomb-group repressive complex 1 (PRC1), see Polycomb-group proteins.
PRC1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases PRC1, ASE1, protein regulator of cytokinesis 1
External IDs MGI: 1858961 HomoloGene: 37868 GeneCards: PRC1
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez

9055

233406

Ensembl

ENSG00000198901

ENSMUSG00000038943

UniProt

O43663

Q99K43

RefSeq (mRNA)

NM_001267580
NM_003981
NM_199413
NM_199414

NM_001285997
NM_001285998
NM_145150

RefSeq (protein)

NP_001254509.1
NP_003972.1

NP_001272926.1

Location (UCSC) Chr 15: 90.97 – 91 Mb Chr 7: 80.29 – 80.32 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/Edit Mouse

Protein Regulator of cytokinesis 1 (PRC1) is a protein that in humans is encoded by the PRC1 gene and is involved in cytokinesis.[3][4]

Function

PRC1 protein is expressed at relatively high levels during S and G2/M phases of the cell cycle before dropping dramatically after mitotic exit and entrance into G1 phase. PRC1 is located in the nucleus during interphase, becomes associated with the mitotic spindle in a highly dynamic manner during anaphase, and localizes to the cell midbody during cytokinesis. PRC1 was first identified in 1998 using and ''in vitro'' phosphorylation screening method and shown to be a substrate of several cyclin-dependent kinases (CDKs).[3] Correspondingly, ablation of PRC1 has been shown to disrupt spindle midzone assembly in mammalian systems.[5]

At least three alternatively spliced transcript variants encoding distinct isoforms of PRC1 have been observed.[4] Additionally, PRC1 has sequence homology with Ase1 in yeasts, SPD-1 (spindle defective 1) in C. elegans, Feo in D. melanogaster, and MAP65 in plants, all of which fall in a conserved family of nonmotor microtubule-associated proteins (MAPs).[6][7][8]

Structure

The crystal structure of PRC1 has only recently been characterized in vitro. In 2013, PRC1 was illustrated as a lengthy molecule consisting of a C-terminal spectrin microtubule-binding domain, an extended rod domain, and an N-terminal dimerization domain.[7][9] Consisting of an intricate arrangement of α-helices, the rod domain, together with the dimerization-conducting N terminus cooperate to facilitate binding of other proteins, such as Kinesin-4, to PRC1. PRC1’s rod domain adopts multiple conformations, all affected by its C-terminal spectrin domain. A model has been suggested in which PRC1 is likely to be a flexible molecule both in solution and on single microtubules but becomes more rigid when the microtubule-binding domains are restricted with antiparallel microtubule filament crosslinking, seen at the spindle midzone. The overall structure of the PRC1 homodimer is reminiscent of actin-bundling proteins, and this process of microtubule filament crosslinking is similar to that of actin.[7]

Role in cytokinesis

PRC1’s role in midzone microtubule formation, essential to the cytokinetic machinery of mammals, is made possible through its collaboration with Kinesin-4 in setting up a controlled zone of overlapping, antiparallel microtubules at the spindle midzone.[10] PRC1 is normally inhibited until anaphase onset by CDK1 mediated phosphorylation, preventing its dimerization. Upon anaphase onset and removal of inhibitory CDK1 phosphorylation, PRC1 dimers form. These homodimers specifically recognize antiparallel microtubule overlaps, found at the spindle midzone, and bind, allowing microtubule sliding, cross-linking of microtubule filaments, and assembly of central-spindle-mediating proteins, including but not limited to Kinesin-4.[10][11]

PRC1 dimers, required for the high-affinity interaction with Kinesin-4, recruit Kinesin-4 to regions of antiparallel microtubule overlap, where Kinesin-4, a plus-end directed motor protein that inhibits microtubule dynamics, helps to form length-dependent end tags that help stabilize and regulate spindle microtubule assembly within cytokinesis.[7][10] This PRC1-Kinesin-4 complex differentially identifies and regulates the spindle midzone microtubules during cell division.[10] This regulation is crucial in order for cytokinesis to progress properly.

Interactions

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. 1 2 Jiang W, Jimenez G, Wells NJ, Hope TJ, Wahl GM, Hunter T, Fukunaga R (1998). "PRC1: a human mitotic spindle-associated CDK substrate protein required for cytokinesis.". Mol. Cell. 2 (6): 877–85. doi:10.1016/S1097-2765(00)80302-0. PMID 9885575.
  4. 1 2 "Entrez Gene: PRC1 protein regulator of cytokinesis 1".
  5. ↑ Eggert US, Mitchison TJ, Field CM (2006). "Animal Cytokinesis: From Parts List to Mechanisms.". Annu. Rev. Biochem. 75: 543–66. doi:10.1146/annurev.biochem.74.082803.133425. PMID 16756502.
  6. ↑ Bieling P, Telley IA, Surrey T (2010). "A Minimal Midzone Protein Module Controls Formation and Length of Antiparallel Microtubule Overlaps.". Cell. 142 (3): 420–32. doi:10.1016/j.cell.2010.06.033. PMID 20691901.
  7. 1 2 3 4 5 Subramanian R, Ti SC, Tan L, Darst SA, Kapoor TM (2013). "Marking and Measuring Single Microtubules by PRC1 and Kinesin-4.". Cell. 154: 377–90. doi:10.1016/j.cell.2013.06.021. PMC 3761943Freely accessible. PMID 23870126.
  8. ↑ Vernì F, Somma MP, Gunsalus KC, Bonaccorsi S, Belloni G, Goldberg ML, Gatti M (2004). "Feo, the Drosophila Homolog of PRC1, Is Required for Central-Spindle Formation and Cytokinesis.". Curr. Biol. 14 (17): 1569–75. doi:10.1016/j.cub.2004.08.054. PMID 15341744.
  9. ↑ Hu CK, Coughlin M, Mitchison TJ (2012). "Midbody assembly and its regulation during cytokinesis.". Mol. Biol. Cell. 23: 1024–34. doi:10.1091/mbc.E11-08-0721. PMC 3302730Freely accessible. PMID 22278743.
  10. 1 2 3 4 5 Bechstedt S, Brouhard GJ (2013). "Motors and MAPs Collaborate to Size Up Microtubules.". Dev. Cell. 26 (2): 118–20. doi:10.1016/j.devcel.2013.07.010. PMID 23906062.
  11. 1 2 Fededa JP, Gerlich DW (2012). "Molecular Control of animal cell cytokinesis". Nat. Cell Biol. 14 (5): 440–7. doi:10.1038/ncb2482. PMID 22552143.
  12. ↑ Subramanian R, Wilson-Kubalek EM, Arthur CP, Bick MJ, Campbell EA, Darst SA, Milligan RA, Kapoor TM (Aug 2010). "Insights into antiparallel microtubule crosslinking by PRC1, a conserved nonmotor microtubule binding protein". Cell. 142 (3): 433–43. doi:10.1016/j.cell.2010.07.012. PMC 2966277Freely accessible. PMID 20691902.
  13. ↑ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (2005). "Towards a proteome-scale map of the human protein-protein interaction network.". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
  14. ↑ Hu CK, Ozlü N, Coughlin M, Steen JJ, Mitchison TJ (2012). "Plk1 negatively regulates PRC1 to prevent premature midzone formation before cytokinesis.". Mol. Biol. Cell. 23 (4): 2702–11. doi:10.1091/mbc.E12-01-0058. PMC 3395659Freely accessible. PMID 22621898.
  15. ↑ Lee KY, Esmaeili B, Zealley B, Mishima M (2015). "Direct interaction between centralspindlin and PRC1 reinforces mechanical resilience of the central spindle". Nature Communications. 6: 7290. doi:10.1038/ncomms8290. PMID 26088160.

Further reading

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