DCTN2

Summary

Gene Symbol: DCTN2
Description: dynactin subunit 2
Alias: DCTN50, DYNAMITIN, HEL-S-77, RBP50, dynactin subunit 2, 50 kDa dynein-associated polypeptide, dynactin 2 (p50), dynactin complex 50 kDa subunit, epididymis secretory protein Li 77, p50 dynamitin
Species: human
Products:     DCTN2

Top Publications

  1. Vancoillie G, Lambert J, Haeghen Y, Westbroek W, Mulder A, Koerten H, et al. Colocalization of dynactin subunits P150Glued and P50 with melanosomes in normal human melanocytes. Pigment Cell Res. 2000;13:449-57 pubmed
  2. Bransfield K, Askham J, Leek J, Robinson P, Mighell A. Phenotypic changes associated with DYNACTIN-2 (DCTN2) over expression characterise SJSA-1 osteosarcoma cells. Mol Carcinog. 2006;45:157-63 pubmed
    DYNACTIN-2 (DCTN2) localises to chromosome 12q13-q15, a region prone to stable amplification in several cancers...
  3. Echeverri C, Paschal B, Vaughan K, Vallee R. Molecular characterization of the 50-kD subunit of dynactin reveals function for the complex in chromosome alignment and spindle organization during mitosis. J Cell Biol. 1996;132:617-33 pubmed
    ..The data also provide direct in vivo evidence for a role for vertebrate dynactin in modulating cytoplasmic dynein binding to an organelle, and implicate both dynactin and dynein in chromosome alignment and spindle organization. ..
  4. Starr D, Williams B, Hays T, Goldberg M. ZW10 helps recruit dynactin and dynein to the kinetochore. J Cell Biol. 1998;142:763-74 pubmed
    ..ZW10's role in the recruitment of dynein to the kinetochore is likely to be reasonably direct, because dynamitin, the p50 subunit of the dynactin complex, interacts with ZW10 in a yeast two-hybrid screen...
  5. Lehmann M, Milev M, Abrahamyan L, Yao X, Pante N, Mouland A. Intracellular transport of human immunodeficiency virus type 1 genomic RNA and viral production are dependent on dynein motor function and late endosome positioning. J Biol Chem. 2009;284:14572-85 pubmed publisher
    ..motor function was disrupted by small interference RNA-mediated depletion of the dynein heavy chain or by p50/dynamitin overexpression...
  6. Hoogenraad C, Akhmanova A, Howell S, Dortland B, De Zeeuw C, Willemsen R, et al. Mammalian Golgi-associated Bicaudal-D2 functions in the dynein-dynactin pathway by interacting with these complexes. EMBO J. 2001;20:4041-54 pubmed
    ..We show here that a mammalian homologue of Bicaudal-D, BICD2, binds to the dynamitin subunit of dynactin...
  7. Tai C, Dujardin D, Faulkner N, Vallee R. Role of dynein, dynactin, and CLIP-170 interactions in LIS1 kinetochore function. J Cell Biol. 2002;156:959-68 pubmed
    ..Displacement of the latter proteins by dynamitin overexpression, however, removes LIS1, suggesting that LIS1 binds to the kinetochore through the motor protein ..
  8. Short B, Preisinger C, Schaletzky J, Kopajtich R, Barr F. The Rab6 GTPase regulates recruitment of the dynactin complex to Golgi membranes. Curr Biol. 2002;12:1792-5 pubmed
    ..Other Golgi Rabs do not bind to dynactin and are unable to support its recruitment to membranes. Rab6 therefore functions as a specificity or tethering factor controlling the recruitment of dynactin to membranes. ..
  9. Motil J, Chan W, Dubey M, Chaudhury P, Pimenta A, Chylinski T, et al. Dynein mediates retrograde neurofilament transport within axons and anterograde delivery of NFs from perikarya into axons: regulation by multiple phosphorylation events. Cell Motil Cytoskeleton. 2006;63:266-86 pubmed
    ..protein-NF-M (GFP-M) and dynein function was inhibited by co-transfection with a construct expressing myc-tagged dynamitin, or by intracellular delivery of purified dynamitin and two antibodies against dynein's cargo domain...

More Information

Publications51

  1. Shen C, Honda H, Suzuki S, Maeda N, Shijo M, Hamasaki H, et al. Dynactin is involved in Lewy body pathology. Neuropathology. 2018;38:583-590 pubmed publisher
    ..dementia with LBs, and multiple system atrophy using immunohistochemistry for p-SNCA, DCTN1, dynactin 2 (DCTN2, dynamitin) and dynein cytoplasmic 1 intermediate chain 1 (DYNC1I1)...
  2. Young J, Stauber T, del Nery E, Vernos I, Pepperkok R, Nilsson T. Regulation of microtubule-dependent recycling at the trans-Golgi network by Rab6A and Rab6A'. Mol Biol Cell. 2005;16:162-77 pubmed
    ..Rab6-directed Golgi-to-ER recycling seems to require functional dynactin, as overexpression of p50/dynamitin, or a C-terminal fragment of Bicaudal-D, both known to interact with dynactin inhibit recycling...
  3. Wang S, Wang Q, Zhang X, Liao X, Wang G, Yu L, et al. Distinct prognostic value of dynactin subunit 4 (DCTN4) and diagnostic value of DCTN1, DCTN2, and DCTN4 in colon adenocarcinoma. Cancer Manag Res. 2018;10:5807-5824 pubmed publisher
    ..The expression levels of DCTN1, DCTN2, and DCTN4 could allow differentiation between cancer-bearing tissues and paracancerous tissue...
  4. Wang Q, Wang X, Liang Q, Wang S, Liao X, Li D, et al. Prognostic Value of Dynactin mRNA Expression in Cutaneous Melanoma. Med Sci Monit. 2018;24:3752-3763 pubmed publisher
    ..RESULTS The multivariate survival analysis showed that individually low expression of DCTN1, DCTN2, and DCTN5 and high expression of DCTN6 were associated with favorable OS (adjusted P=0.008, HR=0.676, 95% CI=0...
  5. Mital J, Lutter E, Barger A, Dooley C, Hackstadt T. Chlamydia trachomatis inclusion membrane protein CT850 interacts with the dynein light chain DYNLT1 (Tctex1). Biochem Biophys Res Commun. 2015;462:165-70 pubmed publisher
    ..substrates of the dynein motor, disruption of the dynactin cargo-linking complex by over-expression of the p50 dynamitin subunit does not inhibit C. trachomatis transport...
  6. Morris E, Assi K, Salh B, Dedhar S. Integrin-linked kinase links dynactin-1/dynactin-2 with cortical integrin receptors to orient the mitotic spindle relative to the substratum. Sci Rep. 2015;5:8389 pubmed publisher
    ..These data demonstrate that ILK is a linker between Integrin receptors and the Dynactin complex to regulate mitotic spindle orientation. ..
  7. Ai E, Poole D, Skop A. RACK-1 directs dynactin-dependent RAB-11 endosomal recycling during mitosis in Caenorhabditis elegans. Mol Biol Cell. 2009;20:1629-38 pubmed publisher
    ..We found that RACK-1 directly binds to DNC-2, the C. elegans p50/dynamitin subunit of the dynactin complex...
  8. Bananis E, Nath S, Gordon K, Satir P, Stockert R, Murray J, et al. Microtubule-dependent movement of late endocytic vesicles in vitro: requirements for Dynein and Kinesin. Mol Biol Cell. 2004;15:3688-97 pubmed
    ..b>Dynamitin antibodies prevented the association of late vesicles with microtubules...
  9. Ahmad F, Echeverri C, Vallee R, Baas P. Cytoplasmic dynein and dynactin are required for the transport of microtubules into the axon. J Cell Biol. 1998;140:391-401 pubmed
    ..dynein is the motor protein that drives this transport, we experimentally increased the levels of the dynamitin subunit of dynactin within the neurons...
  10. Horníková L, Fraiberk M, Man P, Janovec V, Forstova J. VP1, the major capsid protein of the mouse polyomavirus, binds microtubules, promotes their acetylation and blocks the host cell cycle. FEBS J. 2017;284:301-323 pubmed publisher
    ..Dynein is not responsible for the VP1-microtubule association, as neither overexpression of p53/dynamitin nor treatment with ciliobrevin-D (an inhibitor of dynein activity) prevented binding of VP1 to microtubules...
  11. An L, Li G, Si J, Zhang C, Han X, Wang S, et al. Acrylamide Retards the Slow Axonal Transport of Neurofilaments in Rat Cultured Dorsal Root Ganglia Neurons and the Corresponding Mechanisms. Neurochem Res. 2016;41:1000-9 pubmed publisher
    ..mechanisms exploration, the protein level of neurofilament subunits, motor proteins kinesin and dynein, and dynamitin subunit of dynactin in DRG neurons were assessed by western blotting and the concentrations of ATP was detected ..
  12. Liu G, Sanghavi P, Bollinger K, Perry L, Marshall B, Roon P, et al. Efficient Endocytic Uptake and Maturation in Drosophila Oocytes Requires Dynamitin/p50. Genetics. 2015;201:631-49 pubmed publisher
    ..A central component of this complex is Dynamitin/p50 (Dmn). Dmn is required for endosome motility in mammalian cell lines...
  13. Jeong Y, Her J, Oh S, Chung I. Hsp90-binding immunophilin FKBP52 modulates telomerase activity by promoting the cytoplasmic retrotransport of hTERT. Biochem J. 2016;473:3517-3532 pubmed
    ..with the hTERT-Hsp90 complex through binding of the tetratricopeptide repeat domain to Hsp90 and binding of the dynamitin (Dyt) component of the dynein-associated dynactin complex to the peptidyl prolyl isomerase domain...
  14. Wu C, Zong Q, Du A, Zhang W, Yao H, Yu X, et al. Knockdown of Dynamitin in testes significantly decreased male fertility in Drosophila melanogaster. Dev Biol. 2016;420:79-89 pubmed publisher
    b>Dynamitin (Dmn) is a major component of dynactin, a multiprotein complex playing important roles in a variety of intracellular motile events. We previously found that Wolbachia bacterial infection resulted in a reduction of Dmn protein...
  15. Kunoh T, Noda T, Koseki K, Sekigawa M, Takagi M, Shin ya K, et al. A novel human dynactin-associated protein, dynAP, promotes activation of Akt, and ergosterol-related compounds induce dynAP-dependent apoptosis of human cancer cells. Mol Cancer Ther. 2010;9:2934-42 pubmed publisher
    ..Taken together, dynAP can be a new target for cancer therapy, and the selected chemicals are useful for developing a new class of anticancer drugs. ..
  16. Jacquot G, Maidou Peindara P, Benichou S. Molecular and functional basis for the scaffolding role of the p50/dynamitin subunit of the microtubule-associated dynactin complex. J Biol Chem. 2010;285:23019-31 pubmed publisher
    p50/dynamitin (DM) is a major subunit of the microtubule-associated dynactin complex that is required for stabilization and attachment of its two distinct structural domains, namely the Arp1 rod and the shoulder/sidearm...
  17. Karki S, Tokito M, Holzbaur E. A dynactin subunit with a highly conserved cysteine-rich motif interacts directly with Arp1. J Biol Chem. 2000;275:4834-9 pubmed
  18. Berrueta L, Tirnauer J, Schuyler S, Pellman D, Bierer B. The APC-associated protein EB1 associates with components of the dynactin complex and cytoplasmic dynein intermediate chain. Curr Biol. 1999;9:425-8 pubmed
    ..EB1 was also found associated with the intermediate chain of cytoplasmic dynein (CDIC) and with dynamitin (p50), another component of the dynactin complex, but not with dynein heavy chain, in a complex that sedimented ..
  19. Brocard C, Boucher K, Jedeszko C, Kim P, Walton P. Requirement for microtubules and dynein motors in the earliest stages of peroxisome biogenesis. Traffic. 2005;6:386-95 pubmed
  20. Camargo L, Collura V, Rain J, Mizuguchi K, Hermjakob H, Kerrien S, et al. Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia. Mol Psychiatry. 2007;12:74-86 pubmed
  21. Uetake Y, Terada Y, Matuliene J, Kuriyama R. Interaction of Cep135 with a p50 dynactin subunit in mammalian centrosomes. Cell Motil Cytoskeleton. 2004;58:53-66 pubmed
    ..156:87-99]. To identify Cep135-interacting molecules, we screened yeast two-hybrid libraries. One clone encoded dynamitin, a p50 dynactin subunit, which localized at the centrosome and has been shown to be involved in anchoring ..
  22. Choi W, Khurana A, Mathur R, Viswanathan V, Steele D, Fedida D. Kv1.5 surface expression is modulated by retrograde trafficking of newly endocytosed channels by the dynein motor. Circ Res. 2005;97:363-71 pubmed
    ..5. Overexpression of p50/dynamitin, known to disrupt the dynein-dynactin complex responsible for carrying vesicle cargo, substantially increased ..
  23. Ficarro S, Salomon A, Brill L, Mason D, Stettler Gill M, Brock A, et al. Automated immobilized metal affinity chromatography/nano-liquid chromatography/electrospray ionization mass spectrometry platform for profiling protein phosphorylation sites. Rapid Commun Mass Spectrom. 2005;19:57-71 pubmed
  24. Yue L, Lu S, Garces J, Jin T, Li J. Protein kinase C-regulated dynamitin-macrophage-enriched myristoylated alanine-rice C kinase substrate interaction is involved in macrophage cell spreading. J Biol Chem. 2000;275:23948-56 pubmed
    ..The mechanism of involvement of the microtubules and PKC in this event is not fully understood. Dynamitin is a subunit of dynactin, which is important for linking the microtubule-dependent motor protein dynein to ..
  25. Khanna H, Hurd T, Lillo C, Shu X, Parapuram S, He S, et al. RPGR-ORF15, which is mutated in retinitis pigmentosa, associates with SMC1, SMC3, and microtubule transport proteins. J Biol Chem. 2005;280:33580-7 pubmed
    ..transport polypeptide IFT88 as well as microtubule motor proteins, including KIF3A, p150Glued, and p50-dynamitin. Inhibition of dynein function by overexpressing p50 abrogated the localization of RPGR-ORF15 to basal bodies...
  26. Chatin B, Colombier P, Gamblin A, Allouis M, Le Bouffant F. Dynamitin affects cell-surface expression of voltage-gated sodium channel Nav1.5. Biochem J. 2014;463:339-49 pubmed publisher
    ..Using a yeast two-hybrid screen, we identified dynamitin as a Nav1.5-interacting protein. Dynamitin is part of the microtubule-binding multiprotein complex dynactin...
  27. Staples C, Myers K, Beveridge R, Patil A, Howard A, Barone G, et al. Ccdc13 is a novel human centriolar satellite protein required for ciliogenesis and genome stability. J Cell Sci. 2014;127:2910-9 pubmed publisher
  28. Eckley D, Gill S, Melkonian K, Bingham J, Goodson H, Heuser J, et al. Analysis of dynactin subcomplexes reveals a novel actin-related protein associated with the arp1 minifilament pointed end. J Cell Biol. 1999;147:307-20 pubmed
    ..Treatment of purified dynactin with recombinant dynamitin yields two assemblies: the actin-related protein, Arp1, minifilament and the p150(Glued) sidearm...
  29. Fumoto K, Hoogenraad C, Kikuchi A. GSK-3beta-regulated interaction of BICD with dynein is involved in microtubule anchorage at centrosome. EMBO J. 2006;25:5670-82 pubmed
    ..These results imply that GSK-3beta may function in transporting centrosomal proteins to the centrosome by stabilizing the BICD1 and dynein complex, resulting in the regulation of a focused microtubule organization. ..
  30. Maier K, Godfrey J, Echeverri C, Cheong F, Schroer T. Dynamitin mutagenesis reveals protein-protein interactions important for dynactin structure. Traffic. 2008;9:481-91 pubmed publisher
    ..b>Dynamitin (p50) is a core element of dynactin structure...
  31. Zaichick S, Bohannon K, Hughes A, Sollars P, Pickard G, Smith G. The herpesvirus VP1/2 protein is an effector of dynein-mediated capsid transport and neuroinvasion. Cell Host Microbe. 2013;13:193-203 pubmed publisher
    ..Thus, VP1/2 tethers PRV capsids to dynein/dynactin to enhance microtubule transport, neuroinvasion, and pathogenesis...
  32. Valle Tenney R, Opazo T, Cancino J, Goff S, Arriagada G. Dynein Regulators Are Important for Ecotropic Murine Leukemia Virus Infection. J Virol. 2016;90:6896-6905 pubmed publisher
    ..immunoprecipitation and mass spectrometry, we established that the microtubule motor dynein regulator DCTN2/p50/dynamitin interacts with the MLV preintegration complex early in infection, suggesting a direct interaction between the ..
  33. Li X, Rydzewski N, Hider A, Zhang X, Yang J, Wang W, et al. A molecular mechanism to regulate lysosome motility for lysosome positioning and tubulation. Nat Cell Biol. 2016;18:404-17 pubmed publisher
    ..Ca(2+) release from lysosomes thus provides an on-demand mechanism regulating lysosome motility, positioning and tubulation. ..
  34. Wollscheid H, Biancospino M, He F, Magistrati E, Molteni E, Lupia M, et al. Diverse functions of myosin VI elucidated by an isoform-specific α-helix domain. Nat Struct Mol Biol. 2016;23:300-308 pubmed publisher
    ..Thus, the α2-linker acts like a molecular switch that assigns myosin VI to distinct endocytic (myosin VI(long)) or migratory (myosin VI(short)) functional roles. ..
  35. Braathen G, Høyer H, Busk Ã, Tveten K, Skjelbred C, Russell M. Variants in the genes DCTN2, DNAH10, LRIG3, and MYO1A are associated with intermediate Charcot-Marie-Tooth disease in a Norwegian family. Acta Neurol Scand. 2016;134:67-75 pubmed publisher
    ..We investigated whether variants in the DCTN2 could cause CMT...
  36. Pawlica P, Berthoux L. Cytoplasmic dynein promotes HIV-1 uncoating. Viruses. 2014;6:4195-211 pubmed publisher
    ..with dynein function, we depleted dynein heavy chain (DHC) using RNA interference, and we over-expressed p50/dynamitin. In immunofluorescence microscopy experiments, DHC depletion caused an accumulation of CA foci in HIV-1 infected ..
  37. Splinter D, Razafsky D, Schlager M, Serra Marques A, Grigoriev I, Demmers J, et al. BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures. Mol Biol Cell. 2012;23:4226-41 pubmed publisher
    ..Our results demonstrate that dynein recruitment to cargo requires concerted action of multiple dynein cofactors...
  38. Liang Y, Yu W, Li Y, Yang Z, Yan X, Huang Q, et al. Nudel functions in membrane traffic mainly through association with Lis1 and cytoplasmic dynein. J Cell Biol. 2004;164:557-66 pubmed
    ..Together, it is concluded that Nudel is critical for dynein motor activity in membrane transport and possibly other cellular activities through interactions with both Lis1 and dynein heavy chain. ..
  39. Inoue M, Arasaki K, Ueda A, Aoki T, Tagaya M. N-terminal region of ZW10 serves not only as a determinant for localization but also as a link with dynein function. Genes Cells. 2008;13:905-14 pubmed publisher
    ZW10 interacts with dynamitin, a subunit of the dynein accessory complex dynactin, and functions in termination of the spindle checkpoint during mitosis and in membrane transport between the endoplasmic reticulum (ER) and Golgi apparatus ..
  40. Ban K, Torres J, Miller J, Mikhailov A, Nachury M, Tung J, et al. The END network couples spindle pole assembly to inhibition of the anaphase-promoting complex/cyclosome in early mitosis. Dev Cell. 2007;13:29-42 pubmed
    ..The organization of the APC/C on the spindle also provides a framework for understanding microtubule-dependent organization of protein destruction. ..
  41. Watson P, Forster R, Palmer K, Pepperkok R, Stephens D. Coupling of ER exit to microtubules through direct interaction of COPII with dynactin. Nat Cell Biol. 2005;7:48-55 pubmed
    ..Together, our data suggest a mechanism by which membranes of the early secretory pathway can be linked to motors and microtubules for subsequent organization and movement to the Golgi apparatus...
  42. Merdes A, Heald R, Samejima K, Earnshaw W, Cleveland D. Formation of spindle poles by dynein/dynactin-dependent transport of NuMA. J Cell Biol. 2000;149:851-62 pubmed
    ..spindle pole assembly and maintenance, since disruption of the dynactin complex (by increasing the amount of the dynamitin subunit) or dynein function (with an antibody) strongly inhibits NuMA translocation and accumulation and ..