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DCTN2  -  dynactin 2 (p50)

Homo sapiens

Synonyms: 50 kDa dynein-associated polypeptide, DCTN-50, DCTN50, DYNAMITIN, Dynactin complex 50 kDa subunit, ...
 
 
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Disease relevance of DCTN2

 

Psychiatry related information on DCTN2

  • Overexpression of p50/dynamitin, which causes the dissociation of the dynactin complex, significantly inhibited the formation of aggresomes, suggesting that the minus-end-directed motor activities of cytoplasmic dynein are required for aggresome formation [4].
 

High impact information on DCTN2

  • Overexpression of dynamitin or microinjection of anti-dynein antibody before DNA damage abrogates nuclear accumulation of p53 [5].
  • ZW10, a dynamitin-interacting protein associated with kinetochores, is known to participate directly in turning off of the spindle checkpoint [6].
  • Displacement of the latter proteins by dynamitin overexpression, however, removes LIS1, suggesting that LIS1 binds to the kinetochore through the motor protein complexes and may interact with them directly [7].
  • In contrast, the amount of dynamitin is unaltered in these preparations, indicating that it is involved in linking vimentin cargo to dynactin [8].
  • Using a function-blocking antibody as well as dynamitin overexpression, we found that a block in dynein-cargo interaction induced no change in adhesion site dynamics in Xenopus fibroblasts [9].
 

Chemical compound and disease context of DCTN2

 

Biological context of DCTN2

 

Anatomical context of DCTN2

 

Associations of DCTN2 with chemical compounds

  • We report that dynamitin is a Ca(2+)/calmodulin-binding protein and that dynamitin binds directly to macrophage-enriched myristoylated alanine-rice C kinase substrate (MacMARCKS), a membrane-associated PKC substrate involved in macrophage spreading and integrin activation [13].
  • Protein kinase C-regulated dynamitin-macrophage-enriched myristoylated alanine-rice C kinase substrate interaction is involved in macrophage cell spreading [13].
  • 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 at approximately 5S in a sucrose density gradient [15].
  • Golgi-to-ER traffic of stack markers induced by brefeldin A was not inhibited by dynamitin overexpression [14].
  • Inhibition of cytoplasmic dynein based motility by overexpression of the dynactin subunit, dynamitin (p50), inhibited the movement of peroxisomes in vivo and interfered with the reestablishment of a uniform distribution of peroxisomes after recovery from nocodazole treatment [16].
 

Other interactions of DCTN2

 

Analytical, diagnostic and therapeutic context of DCTN2

  • Only SJSA-1 cells were characterised by DCTN2 overexpression on Western blot analyses [1].
  • We find that of 12 distinct dynein and dynactin subunits, the dynein heavy and intermediate chains, as well as dynamitin, interact with the WD repeat region of LIS1 in coexpression/coimmunoprecipitation and two-hybrid assays [7].

References

  1. Phenotypic changes associated with DYNACTIN-2 (DCTN2) over expression characterise SJSA-1 osteosarcoma cells. Bransfield, K.L., Askham, J.M., Leek, J.P., Robinson, P.A., Mighell, A.J. Mol. Carcinog. (2006) [Pubmed]
  2. Function of dynein and dynactin in herpes simplex virus capsid transport. Döhner, K., Wolfstein, A., Prank, U., Echeverri, C., Dujardin, D., Vallee, R., Sodeik, B. Mol. Biol. Cell (2002) [Pubmed]
  3. Chlamydia trachomatis uses host cell dynein to traffic to the microtubule-organizing center in a p50 dynamitin-independent process. Grieshaber, S.S., Grieshaber, N.A., Hackstadt, T. J. Cell. Sci. (2003) [Pubmed]
  4. Characterization and dynamics of aggresome formation by a cytosolic GFP-chimera. García-Mata, R., Bebök, Z., Sorscher, E.J., Sztul, E.S. J. Cell Biol. (1999) [Pubmed]
  5. p53 is associated with cellular microtubules and is transported to the nucleus by dynein. Giannakakou, P., Sackett, D.L., Ward, Y., Webster, K.R., Blagosklonny, M.V., Fojo, T. Nat. Cell Biol. (2000) [Pubmed]
  6. Implication of ZW10 in membrane trafficking between the endoplasmic reticulum and Golgi. Hirose, H., Arasaki, K., Dohmae, N., Takio, K., Hatsuzawa, K., Nagahama, M., Tani, K., Yamamoto, A., Tohyama, M., Tagaya, M. EMBO J. (2004) [Pubmed]
  7. Role of dynein, dynactin, and CLIP-170 interactions in LIS1 kinetochore function. Tai, C.Y., Dujardin, D.L., Faulkner, N.E., Vallee, R.B. J. Cell Biol. (2002) [Pubmed]
  8. A requirement for cytoplasmic dynein and dynactin in intermediate filament network assembly and organization. Helfand, B.T., Mikami, A., Vallee, R.B., Goldman, R.D. J. Cell Biol. (2002) [Pubmed]
  9. Modulation of substrate adhesion dynamics via microtubule targeting requires kinesin-1. Krylyshkina, O., Kaverina, I., Kranewitter, W., Steffen, W., Alonso, M.C., Cross, R.A., Small, J.V. J. Cell Biol. (2002) [Pubmed]
  10. Eg5 is static in bipolar spindles relative to tubulin: evidence for a static spindle matrix. Kapoor, T.M., Mitchison, T.J. J. Cell Biol. (2001) [Pubmed]
  11. In vivo interaction between dynamitin and MacMARCKS detected by the fluorescent resonance energy transfer method. Jin, T., Yue, L., Li, J. J. Biol. Chem. (2001) [Pubmed]
  12. Dynamitin controls Beta 2 integrin avidity by modulating cytoskeletal constraint on integrin molecules. Jin, T., Li, J. J. Biol. Chem. (2002) [Pubmed]
  13. Protein kinase C-regulated dynamitin-macrophage-enriched myristoylated alanine-rice C kinase substrate interaction is involved in macrophage cell spreading. Yue, L., Lu, S., Garces, J., Jin, T., Li, J. J. Biol. Chem. (2000) [Pubmed]
  14. Overexpression of the dynamitin (p50) subunit of the dynactin complex disrupts dynein-dependent maintenance of membrane organelle distribution. Burkhardt, J.K., Echeverri, C.J., Nilsson, T., Vallee, R.B. J. Cell Biol. (1997) [Pubmed]
  15. The APC-associated protein EB1 associates with components of the dynactin complex and cytoplasmic dynein intermediate chain. Berrueta, L., Tirnauer, J.S., Schuyler, S.C., Pellman, D., Bierer, B.E. Curr. Biol. (1999) [Pubmed]
  16. Real time imaging reveals a peroxisomal reticulum in living cells. Schrader, M., King, S.J., Stroh, T.A., Schroer, T.A. J. Cell. Sci. (2000) [Pubmed]
  17. Formation of spindle poles by dynein/dynactin-dependent transport of NuMA. Merdes, A., Heald, R., Samejima, K., Earnshaw, W.C., Cleveland, D.W. J. Cell Biol. (2000) [Pubmed]
  18. RPGR-ORF15, which is mutated in retinitis pigmentosa, associates with SMC1, SMC3, and microtubule transport proteins. Khanna, H., Hurd, T.W., Lillo, C., Shu, X., Parapuram, S.K., He, S., Akimoto, M., Wright, A.F., Margolis, B., Williams, D.S., Swaroop, A. J. Biol. Chem. (2005) [Pubmed]
  19. Human Zwint-1 specifies localization of Zeste White 10 to kinetochores and is essential for mitotic checkpoint signaling. Wang, H., Hu, X., Ding, X., Dou, Z., Yang, Z., Shaw, A.W., Teng, M., Cleveland, D.W., Goldberg, M.L., Niu, L., Yao, X. J. Biol. Chem. (2004) [Pubmed]
 
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