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Gene Review

DLC1  -  DLC1 Rho GTPase activating protein

Homo sapiens

Synonyms: ARHGAP7, DLC-1, Deleted in liver cancer 1 protein, HP, HP protein, ...
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Disease relevance of DLC1


High impact information on DLC1

  • Circannual control of hibernation by HP complex in the brain [6].
  • We report that cten binds to another tumor suppressor, deleted in liver cancer 1 (DLC-1), and the SH2 domain of cten is responsible for the interaction [7].
  • Unexpectedly, the interaction between DLC-1 and the cten SH2 domain is independent of tyrosine phosphorylation of DLC-1 [7].
  • These results provide a novel mechanism whereby the SH2 domain of cten-mediated focal adhesion localization of DLC-1 plays an essential role in its tumor suppression activity [7].
  • Furthermore, Dlc-1 and I kappaB alpha were found to associate with the microtubule organizing center, a perinuclear region from which microtubules radiate [8].

Chemical compound and disease context of DLC1


Biological context of DLC1

  • The delineation of the gene structure allows mutation analysis of DLC1 in other tumour types for which it remains a candidate tumour suppressor gene based on its location and homology to rhoGAP [1].
  • The rarity of exonic missense mutations, and the absence of protein-truncating mutations, indicates that DLC1 is not the target of 8p LOH in colorectal or ovarian tumours [1].
  • We have delineated the structure of the DLC1 gene and used single-stranded conformation polymorphism analysis (SSCP) to look for sequence variants in 126 colorectal and 33 ovarian primary tumours and cell lines [1].
  • Seven informative SNPs that spanned the complete DLC1 gene were genotyped in an additional 249 sporadic cases and 222 unaffected controls [2].
  • The 14-kDa dynein light chain-family protein Dlc1 is required for regular oscillatory nuclear movement and efficient recombination during meiotic prophase in fission yeast [12].

Anatomical context of DLC1


Associations of DLC1 with chemical compounds

  • We identified KIBRA, a WW domain- and a glutamic acid stretch-containing protein, as a DLC1-binding protein and showed that it interacts with DLC1 both in vitro and in vivo [14].
  • Transcriptional silencing of DLC-1 was primarily associated with aberrant DNA methylation, rather than genomic deletion as 5-aza-2'-deoxycytidine induced reactivation of DLC-1 expression in 82% (9/11) NSCLC cell lines showing downregulated DLC-1 [15].
  • Pak1 phosphorylation of DLC1 on Ser-88 controls vesicle formation and trafficking functions, as Ser-88 substitution for alanine prevents macropinocytosis [16].
  • Recent studies have identified dynein light chain-1 (DLC1), a component of the dynein motor, as a p21-activated kinase 1 (Pak1)-interacting substrate with binding sites mapped to amino acids 61-89 of DLC1 and phosphorylation site at serine 88 [16].
  • Pak1 associates with the complex of DLC1 and BimL, a proapoptotic BH3-only protein, and phosphorylates both proteins [17].
  • We further show that treatment of cells with phorbol ester or coexpression of 14-3-3 proteins, blocks DLC1 nucleocytoplasmic shuttling, probably by masking a previously unrecognized nuclear localization sequence [18].

Enzymatic interactions of DLC1


Regulatory relationships of DLC1


Other interactions of DLC1


Analytical, diagnostic and therapeutic context of DLC1


  1. Sequence variants of DLC1 in colorectal and ovarian tumours. Wilson, P.J., McGlinn, E., Marsh, A., Evans, T., Arnold, J., Wright, K., Biden, K., Young, J., Wainwright, B., Wicking, C., Chenevix-Trench, G. Hum. Mutat. (2000) [Pubmed]
  2. Evaluation of DLC1 as a prostate cancer susceptibility gene: mutation screen and association study. Zheng, S.L., Mychaleckyj, J.C., Hawkins, G.A., Isaacs, S.D., Wiley, K.E., Turner, A., Chang, B.L., von Kap-Herr, C., Carpten, J.D., Pettenati, M., Bleecker, E.R., Walsh, P.C., Trent, J.M., Meyers, D.A., Isaacs, W.B., Xu, J. Mutat. Res. (2003) [Pubmed]
  3. Dynein light chain 1 contributes to cell cycle progression by increasing cyclin-dependent kinase 2 activity in estrogen-stimulated cells. den Hollander, P., Kumar, R. Cancer Res. (2006) [Pubmed]
  4. DLC1 is unlikely to be a primary target for deletions on chromosome arm 8p22 in head and neck squamous cell carcinoma. Hewitt, C., Wilson, P., McGlinn, E., MacFarlane, G., Papageorgiou, A., Woodwards, R.T., Sloan, P., Gollin, S.M., Paterson, I., Parkinson, K.K., Read, A.P., Thakker, N. Cancer Lett. (2004) [Pubmed]
  5. The major 8p22 tumor suppressor DLC1 is frequently silenced by methylation in both endemic and sporadic nasopharyngeal, esophageal, and cervical carcinomas, and inhibits tumor cell colony formation. Seng, T.J., Low, J.S., Li, H., Cui, Y., Goh, H.K., Wong, M.L., Srivastava, G., Sidransky, D., Califano, J., Steenbergen, R.D., Rha, S.Y., Tan, J., Hsieh, W.S., Ambinder, R.F., Lin, X., Chan, A.T., Tao, Q. Oncogene (2007) [Pubmed]
  6. Circannual control of hibernation by HP complex in the brain. Kondo, N., Sekijima, T., Kondo, J., Takamatsu, N., Tohya, K., Ohtsu, T. Cell (2006) [Pubmed]
  7. The phosphotyrosine-independent interaction of DLC-1 and the SH2 domain of cten regulates focal adhesion localization and growth suppression activity of DLC-1. Liao, Y.C., Si, L., Devere White, R.W., Lo, S.H. J. Cell Biol. (2007) [Pubmed]
  8. I kappaB alpha physically interacts with a cytoskeleton-associated protein through its signal response domain. Crépieux, P., Kwon, H., Leclerc, N., Spencer, W., Richard, S., Lin, R., Hiscott, J. Mol. Cell. Biol. (1997) [Pubmed]
  9. Transcriptional silencing of the DLC-1 tumor suppressor gene by epigenetic mechanism in gastric cancer cells. Kim, T.Y., Jong, H.S., Song, S.H., Dimtchev, A., Jeong, S.J., Lee, J.W., Kim, T.Y., Kim, N.K., Jung, M., Bang, Y.J. Oncogene (2003) [Pubmed]
  10. Bismuth subsalicylate instead of metronidazole with lansoprazole and clarithromycin for Helicobacter pylori infection: a randomized trial. Chey, W.D., Fisher, L., Elta, G.H., Barnett, J.L., Nostrant, T., DelValle, J., Hasler, W.L., Scheiman, J.M. Am. J. Gastroenterol. (1997) [Pubmed]
  11. The use of hexazonium-p-rosanilin in the histochemical demonstration of peptidases. Lojda, Z. Histochemistry (1975) [Pubmed]
  12. The 14-kDa dynein light chain-family protein Dlc1 is required for regular oscillatory nuclear movement and efficient recombination during meiotic prophase in fission yeast. Miki, F., Okazaki, K., Shimanuki, M., Yamamoto, A., Hiraoka, Y., Niwa, O. Mol. Biol. Cell (2002) [Pubmed]
  13. Interaction of deleted in liver cancer 1 with tensin2 in caveolae and implications in tumor suppression. Yam, J.W., Ko, F.C., Chan, C.Y., Jin, D.Y., Ng, I.O. Cancer Res. (2006) [Pubmed]
  14. Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. Rayala, S.K., den Hollander, P., Manavathi, B., Talukder, A.H., Song, C., Peng, S., Barnekow, A., Kremerskothen, J., Kumar, R. J. Biol. Chem. (2006) [Pubmed]
  15. DLC-1 operates as a tumor suppressor gene in human non-small cell lung carcinomas. Yuan, B.Z., Jefferson, A.M., Baldwin, K.T., Thorgeirsson, S.S., Popescu, N.C., Reynolds, S.H. Oncogene (2004) [Pubmed]
  16. Dynein light chain 1 phosphorylation controls macropinocytosis. Yang, Z., Vadlamudi, R.K., Kumar, R. J. Biol. Chem. (2005) [Pubmed]
  17. Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. Vadlamudi, R.K., Bagheri-Yarmand, R., Yang, Z., Balasenthil, S., Nguyen, D., Sahin, A.A., den Hollander, P., Kumar, R. Cancer Cell (2004) [Pubmed]
  18. DLC1 interacts with 14-3-3 proteins to inhibit RhoGAP activity and block nucleocytoplasmic shuttling. Scholz, R.P., Regner, J., Theil, A., Erlmann, P., Holeiter, G., Jähne, R., Schmid, S., Hausser, A., Olayioye, M.A. J. Cell. Sci. (2009) [Pubmed]
  19. Rho GTPase-activating protein deleted in liver cancer suppresses cell proliferation and invasion in hepatocellular carcinoma. Wong, C.M., Yam, J.W., Ching, Y.P., Yau, T.O., Leung, T.H., Jin, D.Y., Ng, I.O. Cancer Res. (2005) [Pubmed]
  20. Genetic and epigenetic alterations of DLC-1 gene in hepatocellular carcinoma. Wong, C.M., Lee, J.M., Ching, Y.P., Jin, D.Y., Ng, I.O. Cancer Res. (2003) [Pubmed]
  21. Aberrant methylation and deacetylation of deleted in liver cancer-1 gene in prostate cancer: potential clinical applications. Guan, M., Zhou, X., Soulitzis, N., Spandidos, D.A., Popescu, N.C. Clin. Cancer Res. (2006) [Pubmed]
  22. Cloning, characterization, and chromosomal localization of a gene frequently deleted in human liver cancer (DLC-1) homologous to rat RhoGAP. Yuan, B.Z., Miller, M.J., Keck, C.L., Zimonjic, D.B., Thorgeirsson, S.S., Popescu, N.C. Cancer Res. (1998) [Pubmed]
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