ZW10

Last updated
ZW10
Identifiers
Aliases ZW10 , HKNTC1AP, zw10 kinetochore protein
External IDs OMIM: 603954; MGI: 1349478; HomoloGene: 37959; GeneCards: ZW10; OMA:ZW10 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004724

NM_012039

RefSeq (protein)

NP_004715

NP_036169

Location (UCSC) Chr 11: 113.73 – 113.77 Mb Chr 9: 48.97 – 48.99 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Centromere/kinetochore protein zw10 homolog is a protein that in humans is encoded by the ZW10 gene. [5] [6] This gene encodes a protein that is one of many involved in mechanisms to ensure proper chromosome segregation during cell division. The encoded protein binds to centromeres during the prophase, metaphase, and early anaphase cell division stages and to kinetochore microtubules during metaphase. [6]

Contents

Function

Zw10
Identifiers
SymbolZw10
Pfam PF06248
Pfam clan CL0295
InterPro IPR009361
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

Zeste white 10 (ZW10) was initially identified as a mitotic checkpoint protein involved in chromosome segregation, and then implicated in targeting cytoplasmic dynein and dynactin to mitotic kinetochores, but it is also important in non-dividing cells. These include cytoplasmic dynein targeting to Golgi and other membranes, and SNARE-mediated ER-Golgi trafficking. [7] [8] Dominant-negative ZW10, anti-ZW10 antibody, and ZW10 RNA interference (RNAi) cause Golgi dispersal. ZW10 RNAi also disperse endosomes and lysosomes. [8]

Drosophila kinetochore components Rough deal (Rod) and Zw10 are required for the proper functioning of the metaphase checkpoint in flies. [9] The eukaryotic spindle assembly checkpoint (SAC) monitors microtubule attachment to kinetochores and prevents anaphase onset until all kinetochores are aligned on the metaphase plate. It is an essential surveillance mechanism that ensures high fidelity chromosome segregation during mitosis. In higher eukaryotes, cytoplasmic dynein is involved in silencing the SAC by removing the checkpoint proteins Mad2 and the Rod-Zw10-Zwilch complex (RZZ) from aligned kinetochores. [10] [11] [12]

Interactions

ZW10 has been shown to interact with RINT1 [13] and dynamitin. [14]

Related Research Articles

<span class="mw-page-title-main">Spindle apparatus</span> Feature of biological cell structure

In cell biology, the spindle apparatus is the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.

<span class="mw-page-title-main">Dynein</span> Class of enzymes

Dyneins are a family of cytoskeletal motor proteins that move along microtubules in cells. They convert the chemical energy stored in ATP to mechanical work. Dynein transports various cellular cargos, provides forces and displacements important in mitosis, and drives the beat of eukaryotic cilia and flagella. All of these functions rely on dynein's ability to move towards the minus-end of the microtubules, known as retrograde transport; thus, they are called "minus-end directed motors". In contrast, most kinesin motor proteins move toward the microtubules' plus-end, in what is called anterograde transport.

<span class="mw-page-title-main">Spindle checkpoint</span> Cell cycle checkpoint

The spindle checkpoint, also known as the metaphase-to-anaphase transition, the spindle assembly checkpoint (SAC), the metaphase checkpoint, or the mitotic checkpoint, is a cell cycle checkpoint during metaphase of mitosis or meiosis that prevents the separation of the duplicated chromosomes (anaphase) until each chromosome is properly attached to the spindle. To achieve proper segregation, the two kinetochores on the sister chromatids must be attached to opposite spindle poles. Only this pattern of attachment will ensure that each daughter cell receives one copy of the chromosome. The defining biochemical feature of this checkpoint is the stimulation of the anaphase-promoting complex by M-phase cyclin-CDK complexes, which in turn causes the proteolytic destruction of cyclins and proteins that hold the sister chromatids together.

<span class="mw-page-title-main">Kinetochore</span> Protein complex that allows microtubules to attach to chromosomes during cell division

A kinetochore is a disc-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers attach during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere and links the chromosome to microtubule polymers from the mitotic spindle during mitosis and meiosis. The term kinetochore was first used in a footnote in a 1934 Cytology book by Lester W. Sharp and commonly accepted in 1936. Sharp's footnote reads: "The convenient term kinetochore has been suggested to the author by J. A. Moore", likely referring to John Alexander Moore who had joined Columbia University as a freshman in 1932.

<span class="mw-page-title-main">Aurora kinase B</span> Protein

Aurora kinase B is a protein that functions in the attachment of the mitotic spindle to the centromere and in cytokinesis.

<span class="mw-page-title-main">DCTN1</span> Protein-coding gene in the species Homo sapiens

Dynactin subunit 1 is a protein that in humans is encoded by the DCTN1 gene.

<span class="mw-page-title-main">BUB1B</span> Protein-coding gene in the species Homo sapiens

Mitotic checkpoint serine/threonine-protein kinase BUB1 beta is an enzyme that in humans is encoded by the BUB1B gene. Also known as BubR1, this protein is recognized for its mitotic roles in the spindle assembly checkpoint (SAC) and kinetochore-microtubule interactions that facilitate chromosome migration and alignment. BubR1 promotes mitotic fidelity and protects against aneuploidy by ensuring proper chromosome segregation between daughter cells. BubR1 is proposed to prevent tumorigenesis.

<span class="mw-page-title-main">Dynactin</span>

Dynactin is a 23 subunit protein complex that acts as a co-factor for the microtubule motor cytoplasmic dynein-1. It is built around a short filament of actin related protein-1 (Arp1).

<span class="mw-page-title-main">DCTN2</span> Gene of the species Homo sapiens

Dynactin subunit 2 is a protein that in humans is encoded by the DCTN2 gene.

<span class="mw-page-title-main">MAPRE1</span> Protein-coding gene in the species Homo sapiens

Microtubule-associated protein RP/EB family member 1 is a protein that in humans is encoded by the MAPRE1 gene.

<span class="mw-page-title-main">ACTR1A</span> Protein-coding gene in the species Homo sapiens

Alpha-centractin (yeast) or ARP1 is a protein that in humans is encoded by the ACTR1A gene.

<span class="mw-page-title-main">DYNC1H1</span> Protein-coding gene in the species Homo sapiens

Cytoplasmic dynein 1 heavy chain 1 is a protein that in humans is encoded by the DYNC1H1 gene. Dynein is a molecular motor protein that is responsible for the transport of numerous cellular cargoes to minus ends of microtubules, which are typically found in the center of a cell, or the cell body of neurons. It is located on the 14th chromosome at position 14q32.31. Cytoplasmic dynein transports cargoes along the axon in the retrograde direction, bringing materials from the axon to the cell body. Dynein heavy chain binds microtubules and hydrolyzes ATP at its C-terminal head. It binds cargo via interaction with other dynein subunits at its N-terminal tail.

<span class="mw-page-title-main">Centromere protein E</span> Centromere- and microtubule-associated protein

Centromere-associated protein E is a protein that in humans is encoded by the CENPE gene.

<span class="mw-page-title-main">NUF2</span> Protein-coding gene in the species Homo sapiens

Kinetochore protein Nuf2 is a protein that in humans is encoded by the NUF2 gene.

<span class="mw-page-title-main">CLASP2</span> Protein-coding gene in the species Homo sapiens

Cytoplasmic linker associated protein 2, also known as CLASP2, is a protein which in humans is encoded by the CLASP2 gene.

<span class="mw-page-title-main">ZWINT</span> Protein-coding gene in the species Homo sapiens

ZW10 interactor (Zwint-1) is a protein that in humans is encoded by the ZWINT gene.

<span class="mw-page-title-main">DCTN3</span> Protein-coding gene in the species Homo sapiens

Dynactin subunit 3 is a protein that in humans is encoded by the DCTN3 gene.

<span class="mw-page-title-main">Mad1</span>

Mad1 is a non-essential protein which in yeast has a function in the spindle assembly checkpoint (SAC). This checkpoint monitors chromosome attachment to spindle microtubules and prevents cells from starting anaphase until the spindle is built up. The name Mad refers to the observation that mutant cells are mitotic arrest deficient (MAD) during microtubule depolymerization. Mad1 recruits the anaphase inhibitor Mad2 to unattached kinetochores and is essential for Mad2-Cdc20 complex formation in vivo but not in vitro. In vivo, Mad1 acts as a competitive inhibitor of the Mad2-Cdc20 complex. Mad1 is phosphorylated by Mps1 which then leads together with other activities to the formation of the mitotic checkpoint complex (MCC). Thereby it inhibits the activity of the anaphase-promoting complex/cyclosome (APC/C). Homologues of Mad1 are conserved in eukaryotes from yeast to mammals.

In molecular biology, DCTN6 is that subunit of the dynactin protein complex that is encoded by the p27 gene. Dynactin is the essential component for microtubule-based cytoplasmic dynein motor activity in intracellular transport of a variety of cargoes and organelles.

J. Richard McIntosh is a Distinguished Professor Emeritus in Molecular, Cellular, and Developmental Biology at the University of Colorado Boulder. McIntosh first graduated from Harvard with a BA in Physics in 1961, and again with a Ph.D. in Biophysics in 1968. He began his teaching career at Harvard but has spent most of his career at the University of Colorado Boulder. At the University of Colorado Boulder, McIntosh taught biology courses at both the undergraduate and graduate levels. Additionally, he created an undergraduate course in the biology of cancer towards the last several years of his teaching career. McIntosh's research career looks at a variety of things, including different parts of mitosis, microtubules, and motor proteins.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000086827 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000032264 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Starr DA, Williams BC, Li Z, Etemad-Moghadam B, Dawe RK, Goldberg ML (Oct 1997). "Conservation of the centromere/kinetochore protein ZW10". J Cell Biol. 138 (6): 1289–301. doi:10.1083/jcb.138.6.1289. PMC   2132553 . PMID   9298984.
  6. 1 2 "Entrez Gene: ZW10 ZW10, kinetochore associated, homolog (Drosophila)".
  7. Vallee RB, Varma D, Dujardin DL (November 2006). "ZW10 function in mitotic checkpoint control, dynein targeting and membrane trafficking: is dynein the unifying theme?". Cell Cycle. 5 (21): 2447–51. doi:10.4161/cc.5.21.3395. PMC   2794429 . PMID   17102640.
  8. 1 2 Varma D, Dujardin DL, Stehman SA, Vallee RB (February 2006). "Role of the kinetochore/cell cycle checkpoint protein ZW10 in interphase cytoplasmic dynein function". J. Cell Biol. 172 (5): 655–62. doi:10.1083/jcb.200510120. PMC   2063698 . PMID   16505164.
  9. Basto R, Gomes R, Karess RE (December 2000). "Rough deal and Zw10 are required for the metaphase checkpoint in Drosophila". Nat. Cell Biol. 2 (12): 939–43. doi:10.1038/35046592. PMID   11146659. S2CID   27007621.
  10. Griffis ER, Stuurman N, Vale RD (June 2007). "Spindly, a novel protein essential for silencing the spindle assembly checkpoint, recruits dynein to the kinetochore". J. Cell Biol. 177 (6): 1005–15. doi:10.1083/jcb.200702062. PMC   2064361 . PMID   17576797.
  11. Famulski JK, Vos L, Sun X, Chan G (February 2008). "Stable hZW10 kinetochore residency, mediated by hZwint-1 interaction, is essential for the mitotic checkpoint". J. Cell Biol. 180 (3): 507–20. doi:10.1083/jcb.200708021. PMC   2234252 . PMID   18268100.
  12. Yang Z, Tulu US, Wadsworth P, Rieder CL (June 2007). "Kinetochore dynein is required for chromosome motion and congression independent of the spindle checkpoint". Curr. Biol. 17 (11): 973–80. Bibcode:2007CBio...17..973Y. doi:10.1016/j.cub.2007.04.056. PMC   2570756 . PMID   17509882.
  13. Hirose H, Arasaki K, Dohmae N, Takio K, Hatsuzawa K, Nagahama M, Tani K, Yamamoto A, Tohyama M, Tagaya M (March 2004). "Implication of ZW10 in membrane trafficking between the endoplasmic reticulum and Golgi". EMBO J. 23 (6): 1267–78. doi:10.1038/sj.emboj.7600135. PMC   381410 . PMID   15029241.
  14. Starr DA, Williams BC, Hays TS, Goldberg ML (1998). "ZW10 Helps Recruit Dynactin and Dynein to the Kinetochore". Journal of Cell Biology. 142 (3): 763–774. doi: 10.1083/jcb.142.3.763 . PMC   2148168 . PMID   9700164.

Further reading