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Gene Review

RAB8A  -  RAB8A, member RAS oncogene family

Homo sapiens

Synonyms: MEL, Oncogene c-mel, RAB8, Ras-related protein Rab-8A
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Disease relevance of RAB8A


Psychiatry related information on RAB8A

  • Since the overall consistency of significant results was more pronounced in the subjective than in the objective part of the MEL the results fit best a circular pathogenetic model of interactions between life events, their individual evaluation by the patient, and depressive symptoms [6].
  • In NMU-induced mammary carcinogenesis MEL lowered the tumour volume (although statistically non-significantly) by 30% in comparison with the control group; in DMBA-induced mammary carcinogenesis it lowered the tumour volume (2.70 +/- 0.81 cm3 vs. 0.90 +/- 0.33 cm3) and lengthened (non-significantly) the latency period (by 12 days) [7].

High impact information on RAB8A

  • Analysis of human hemoglobin switching in MEL x human fetal erythroid cell hybrids [8].
  • We suggest that DNA sequences that regulate beta-globin gene transcription during MEL differentiation are located both 5' and 3' to the translation initiation site [9].
  • We introduced into MEL cells rabbit beta-globin gene deletion mutants and two sets of hybrid genes constructed from the inducible human beta-globin gene and noninducible human gamma-globin gene or the murine H-2Kbm1 class I MHC gene [9].
  • S1 nuclease analysis of gene transcripts before and after MEL differentiation showed that induction of the rabbit beta-globin gene did not require more than 58 bp of DNA 5' to the transcription initiation site [9].
  • MEL 14, a monoclonal antibody directed against this adhesion molecule, blocks lymphocyte traffic to lymph nodes and extravasation of neutrophils from blood to inflammatory sites [10].

Chemical compound and disease context of RAB8A


Biological context of RAB8A

  • Here we report the identification and the complete cDNA-derived amino acid sequence of a murine rab8-interacting protein (rab8ip) that specifically interacts with rab8 in a GTP-dependent manner [15].
  • We have previously shown that Rab8 controls polarised membrane transport by modulating cell morphogenesis [5] [16].
  • Rab8 has a drastic effect on cell shape, but the membrane trafficking route it regulates is poorly defined [17].
  • Expression of dominant-negative Rab8 mutants or depletion of Rab8 by RNA interference inhibit protrusion formation, but promote cell-cell adhesion and actin stress fiber formation, whereas expression of the constitutively active Rab8-Q67L has the opposite effect [17].
  • Prenylation of Rab8 GTPase by type I and type II geranylgeranyl transferases [18].

Anatomical context of RAB8A


Associations of RAB8A with chemical compounds

  • To determine whether one enzyme plays a predominant role in Rab8 prenylation in vivo, the incorporation of [3H]mevalonate into Rab8 was measured in human embryonal kidney 293 cells under conditions where the activity of GGTaseI, but not GGTaseII, was blocked by the peptidomimetic inhibitor GGTI-298 [18].
  • The modification of Rab8 by GGTaseI did not require REP, indicating that a REP-induced conformational change is not essential for exposure of the Rab carboxyl-terminal cysteine prenylation site [18].
  • The activation of platelets by thrombin, a potent inducer of secretion, resulted in the phosphorylation of rab3B, rab6, and rab8 proteins, whereas no phosphorylation was observed in the presence of prostaglandin E1, which stimulates cAMP-dependent protein kinase and inhibits the secretion process [21].
  • We show here that overexpression of the recycling/exocytic Rab GTPase Rab8 rescued the late endosomal cholesterol deposition and sphingolipid mistrafficking in NPC fibroblasts [11].
  • Our data suggest that in photoreceptors phosphatidylinositol-4,5-bisphosphate, moesin, actin, and rac1 act in concert with rab8 to regulate tethering and fusion of RTCs [22].

Physical interactions of RAB8A

  • The activated form of Rab8 interacted with the amino-terminal region of FIP-2, whereas dominant-negative Rab8 did not [16].

Regulatory relationships of RAB8A

  • We identified a coil-coiled protein (Rabin8), homologous to the rat Rabin3 that stimulated nucleotide exchange on Rab8 but not on Rab3A and Rab5 [23].
  • MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway [24].

Other interactions of RAB8A

  • FIP-2, a coiled-coil protein, links Huntingtin to Rab8 and modulates cellular morphogenesis [16].
  • Furthermore, we show that rat Rabin3 has exchange activity on Rab8 but not on Rab3A, supporting the view that rat Rabin3 is the rat equivalent of human Rabin8 [23].
  • This report demonstrates that Rab8 and Rab13 proteins are isoprenylated in vivo and geranylgeranylated in vitro [25].
  • One protein, rab16, is closely related to members of the rab3 subfamily, whereas two others are assigned as the rat homologs of canine rab8 and rab10 [26].
  • The rab8 GTPase, important for basolateral vesicle targeting, was redistributed from the perinuclear Golgi region to disperse vesicles in ADPKD cells [27].

Analytical, diagnostic and therapeutic context of RAB8A

  • Upon high-performance liquid chromatography (HPLC) gel filtration, melanoma cell-derived IL-1 (MEL-IL-1) exhibited molecular weight heterogeneity, and HPLC chromatofocusing revealed major activity at pH 5.0 and minor activity at pH 7 [28].
  • Low beta 2-microglobulin (beta 2M) levels < or = 2.5 mg/L and MEL 200 therapy were identified as the two most important independent favorable variables associated with prolonged event-free survival (EFS) and overall survival (OS) [4].
  • The MEL sFv-rGel fusion toxin bound to antigen-positive but not antigen-negative cells as assessed by ELISA [29].
  • These results suggest that HERV-K-MEL is a source of antigens that are targeted by CTLs in melanoma patients and could therefore be used for vaccination [5].
  • Nondenaturing gel filtration of MEL extract demonstrated that ErEN is a component of an approximately 160 kDa complex implying that additional proteins may regulate ErEN activity and provide increased cleavage specificity [30].


  1. Rab8, a small GTPase involved in vesicular traffic between the TGN and the basolateral plasma membrane. Huber, L.A., Pimplikar, S., Parton, R.G., Virta, H., Zerial, M., Simons, K. J. Cell Biol. (1993) [Pubmed]
  2. The MEL gene: a new member of the RAB/YPT class of RAS-related genes. Nimmo, E.R., Sanders, P.G., Padua, R.A., Hughes, D., Williamson, R., Johnson, K.J. Oncogene (1991) [Pubmed]
  3. Transfer of genes into hematopoietic cells using recombinant DNA viruses. Karlsson, S., Humphries, R.K., Gluzman, Y., Nienhuis, A.W. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  4. High-dose therapy for refractory multiple myeloma: improved prognosis with better supportive care and double transplants. Vesole, D.H., Barlogie, B., Jagannath, S., Cheson, B., Tricot, G., Alexanian, R., Crowley, J. Blood (1994) [Pubmed]
  5. A human endogenous retroviral sequence encoding an antigen recognized on melanoma by cytolytic T lymphocytes. Schiavetti, F., Thonnard, J., Colau, D., Boon, T., Coulie, P.G. Cancer Res. (2002) [Pubmed]
  6. Reconfirming the role of life events for the timing of depressive episodes. A two-year prospective follow-up study. Mundt, C., Reck, C., Backenstrass, M., Kronmüller, K., Fiedler, P. Journal of affective disorders. (2000) [Pubmed]
  7. Effects of tamoxifen and melatonin on mammary gland cancer induced by N-methyl-N-nitrosourea and by 7,12-dimethylbenz(a)anthracene, respectively, in female Sprague-Dawley rats. Kubatka, P., Bojková, B., M ciková-Kalická, K., Mníchová-Chamilová, M., Adámeková, E., Ahlers, I., Ahlersová, E., Cermáková, M. Folia Biol. (Praha) (2001) [Pubmed]
  8. Analysis of human hemoglobin switching in MEL x human fetal erythroid cell hybrids. Papayannopoulou, T., Brice, M., Stamatoyannopoulos, G. Cell (1986) [Pubmed]
  9. DNA sequences required for regulated expression of beta-globin genes in murine erythroleukemia cells. Wright, S., Rosenthal, A., Flavell, R., Grosveld, F. Cell (1984) [Pubmed]
  10. Neutrophil influx into an inflammatory site inhibited by a soluble homing receptor-IgG chimaera. Watson, S.R., Fennie, C., Lasky, L.A. Nature (1991) [Pubmed]
  11. Rab8-dependent Recycling Promotes Endosomal Cholesterol Removal in Normal and Sphingolipidosis Cells. Linder, M.D., Uronen, R.L., H??ltt??-Vuori, M., van der Sluijs, P., Per??nen, J., Ikonen, E. Mol. Biol. Cell (2007) [Pubmed]
  12. Tyrosine transport in a human melanoma cell line as a basis for selective transport of cytotoxic analogues. Pankovich, J.M., Jimbow, K. Biochem. J. (1991) [Pubmed]
  13. Phase I study for poor-prognosis lymphoma: augmentation of the "BEAM" regimen with escalating dose melphalan using amifostine cytoprotection and autologous hematopoietic stem cell transplantation--a preliminary report. Phillips, G.L., Abboud, C.N., Bernstein, S.H., Friedberg, J.W., Ifthikharuddin, J.J., Lancet, J.E., Liesveld, J.L., Spreng, E., Johnson, V., Chapman, M., Vesole, D.H. Semin. Oncol. (2004) [Pubmed]
  14. Synergistic interactions between interferon beta and carboplatin on SK-MEL 28 human melanoma cell growth inhibition in vitro. Hübner, B., Eckert, K., Garbe, C., Maurer, H.R. J. Cancer Res. Clin. Oncol. (1995) [Pubmed]
  15. In its active form, the GTP-binding protein rab8 interacts with a stress-activated protein kinase. Ren, M., Zeng, J., De Lemos-Chiarandini, C., Rosenfeld, M., Adesnik, M., Sabatini, D.D. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  16. FIP-2, a coiled-coil protein, links Huntingtin to Rab8 and modulates cellular morphogenesis. Hattula, K., Peränen, J. Curr. Biol. (2000) [Pubmed]
  17. Characterization of the Rab8-specific membrane traffic route linked to protrusion formation. Hattula, K., Furuhjelm, J., Tikkanen, J., Tanhuanp????, K., Laakkonen, P., Per??nen, J. J. Cell. Sci. (2006) [Pubmed]
  18. Prenylation of Rab8 GTPase by type I and type II geranylgeranyl transferases. Wilson, A.L., Erdman, R.A., Castellano, F., Maltese, W.A. Biochem. J. (1998) [Pubmed]
  19. Confirmation and refinement of the localisation of the c-MEL locus on chromosome 19 by physical and genetic mapping. Nimmo, E., Padua, R.A., Hughes, D., Brook, J.D., Williamson, R., Johnson, K.J. Hum. Genet. (1989) [Pubmed]
  20. Rab8 promotes polarized membrane transport through reorganization of actin and microtubules in fibroblasts. Peränen, J., Auvinen, P., Virta, H., Wepf, R., Simons, K. J. Cell Biol. (1996) [Pubmed]
  21. Identification of small GTP-binding rab proteins in human platelets: thrombin-induced phosphorylation of rab3B, rab6, and rab8 proteins. Karniguian, A., Zahraoui, A., Tavitian, A. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  22. Phosphoinositides, ezrin/moesin, and rac1 regulate fusion of rhodopsin transport carriers in retinal photoreceptors. Deretic, D., Traverso, V., Parkins, N., Jackson, F., Rodriguez de Turco, E.B., Ransom, N. Mol. Biol. Cell (2004) [Pubmed]
  23. A Rab8-specific GDP/GTP exchange factor is involved in actin remodeling and polarized membrane transport. Hattula, K., Furuhjelm, J., Arffman, A., Peränen, J. Mol. Biol. Cell (2002) [Pubmed]
  24. MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway. Bravo-Cordero, J.J., Marrero-Diaz, R., Megías, D., Genís, L., García-Grande, A., García, M.A., Arroyo, A.G., Montoya, M.C. EMBO J. (2007) [Pubmed]
  25. Isoprenylation of Rab proteins possessing a C-terminal CaaX motif. Joberty, G., Tavitian, A., Zahraoui, A. FEBS Lett. (1993) [Pubmed]
  26. rab15, a novel low molecular weight GTP-binding protein specifically expressed in rat brain. Elferink, L.A., Anzai, K., Scheller, R.H. J. Biol. Chem. (1992) [Pubmed]
  27. ADPKD: a human disease altering Golgi function and basolateral exocytosis in renal epithelia. Charron, A.J., Bacallao, R.L., Wandinger-Ness, A. Traffic (2000) [Pubmed]
  28. Expression and release of interleukin-1 by different human melanoma cell lines. Köck, A., Schwarz, T., Urbanski, A., Peng, Z., Vetterlein, M., Micksche, M., Ansel, J.C., Kung, H.F., Luger, T.A. J. Natl. Cancer Inst. (1989) [Pubmed]
  29. Design, expression, purification, and characterization, in vitro and in vivo, of an antimelanoma single-chain Fv antibody fused to the toxin gelonin. Rosenblum, M.G., Cheung, L.H., Liu, Y., Marks, J.W. Cancer Res. (2003) [Pubmed]
  30. Characterization and purification of a mammalian endoribonuclease specific for the alpha -globin mRNA. Rodgers, N.D., Wang, Z., Kiledjian, M. J. Biol. Chem. (2002) [Pubmed]
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