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Gene Review

RALA  -  v-ral simian leukemia viral oncogene...

Homo sapiens

Synonyms: RAL, Ras-related protein Ral-A
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Disease relevance of RALA

  • Two human cancer cell lines were established from metastatic lesions of an adenocarcinoma (RAL) and a squamous cell (CAEP) carcinoma of the lung [1].
  • Since RAL's estrogen-mimetic effects on human vascular cell growth were independent of MAP-kinase activation and were not affected by hyperglycemia, the potential use of RAL to circumvent the loss of estrogen function induced by hyperglycemia and diabetes in the human vasculature should be further explored [2].
  • As expected from these results in vitro, some of them could prevent the growth of NUGC-3 human gastric cancer cells, and especially RAL was a potent antineoplastic agent with an LD(50) value of 19 microM [3].

High impact information on RALA

  • Because RAL is localized mainly to the Golgi, the expression of the RGR protein was identified in RK13 cells, a cell line that expresses endogenous rgr [4].
  • Here, we show that RALA and RALB collaborate to maintain tumorigenicity through regulation of both proliferation and survival [5].
  • Forty-eight intact (non-ovariectomized) skeletally mature female beagle dogs were treated orally for 12 months with clinically relevant doses of risedronate (RIS, 0.10 mg/kg/day), alendronate (ALN, 0.2 mg/kg/day), raloxifene (RAL, 0.50 mg/kg/day), or saline (VEH, 1 ml/kg/day) [6].
  • Microdamage accumulation in RAL-treated animals was not significantly different than VEH; both RIS and ALN had significantly higher crack surface density compared to VEH [6].
  • Conversely, simultaneous treatment induced an antagonistic effect in both cell lines, and the sequential scheme gemcitabine-->docetaxel produced a weak synergistic effect only in RAL cells [7].

Biological context of RALA

  • One other member of this family, RALA, has been previously mapped to the short arm of human chromosome 7 [8].
  • In particular, chromosome 2 pentasomy and several clonal markers were evident in the RAL cells, whereas a telomeric deletion of chromosome 1, del (1)(q32), was observed in the CAEP cells [1].
  • Computer analysis suggested the presence of a transmembrane segment, 5 potential calcium binding sites, and a RAL motif which corresponds to the HAV motif, the potential site for homophilic interaction of typical cadherins [9].
  • Mean respiratory-related oscillation in systolic blood pressure (pulsus paradoxus) increased significantly under each experimental condition compared with those at baseline (2 +/- 2.3 mm Hg): for RAL, 21 +/- 8.4 mm Hg; for HL, 34 +/- 16.3 mm Hg; for H, 10 +/- 5.4 mm Hg; for VL 26 +/- 13.4 mm Hg [10].
  • The cells were halted at G1 phase in the cell cycle by RAL [3].

Anatomical context of RALA

  • The diterpenoids, especially CA and RAL, promoted the formation of hexagonal-H(II) phases at low temperatures in dielaidoylphosphatidylethanolamine (DEPE) membranes which exhibited a smaller tube-to-tube distance compared to pure phospholipid [11].
  • Whereas, AA-specific DNA adducts were detected in all five urinary tract tissues from five patients (total RAL: 32-251 adducts per 10(9) nucleotides), OTA-related DNA adducts were detectable in two kidneys and one ureter only (total RAL: 1.5-3.7 adducts per 10(9) nucleotides) [12].

Associations of RALA with chemical compounds

  • In C, RALB and RALA, the change in base excess from rest to postexercise was greater than the concomitant increase in blood lactate concentration, suggesting the presence of a significant amount of acid in the blood in addition to lactic acid [13].
  • A serine kinase associates with the RAL GTPase and phosphorylates RAL-interacting protein 1 [14].
  • The photophysical properties of all-trans-retinal (RAL) have been extensively studied because of the importance of the retinoids in the visual process [15].
  • In VSMC, high glucose prevented the inhibitory effect of high E(2) (but not of high RAL) concentrations on DNA synthesis [2].
  • A possible precursor to A2-E is the imine formed from RAL and ethanolamine [16].

Analytical, diagnostic and therapeutic context of RALA

  • The DNA adducts were identified and quantitated by multidimensional chromatography on PEI-TLC sheets by screen enhanced autoradiography and presented as RAL (relative adduct labelling) values [17].
  • Five hundred and eleven carotid endarterectomies were performed over the last 11 years by two of us (JEM and RAL) [18].
  • The antibody reacted specifically with RAL, as demonstrated by the Ouchterlony double diffusion test, immunoelectrophoresis, and SDS polyacrylamide gel electrophoresis of the immunoprecipitate [19].


  1. Molecular and biological features of two new human squamous and adenocarcinoma of the lung cell lines. Gasperi-Campani, A., Roncuzzi, L., Ricotti, L., Lenzi, L., Gruppioni, R., Sensi, A., Zini, N., Zoli, W., Amadori, D. Cancer Genet. Cytogenet. (1998) [Pubmed]
  2. High glucose blocks the effects of estradiol on human vascular cell growth: differential interaction with estradiol and raloxifene. Somjen, D., Paller, C.J., Gayer, B., Kohen, F., Knoll, E., Stern, N. J. Steroid Biochem. Mol. Biol. (2004) [Pubmed]
  3. Vitamin A-related compounds, all-trans retinal and retinoic acids, selectively inhibit activities of mammalian replicative DNA polymerases. Murakami, C., Takemura, M., Sugiyama, Y., Kamisuki, S., Asahara, H., Kawasaki, M., Ishidoh, T., Linn, S., Yoshida, S., Sugawara, F., Yoshida, H., Sakaguchi, K., Mizushina, Y. Biochim. Biophys. Acta (2002) [Pubmed]
  4. rgr oncogene: activation by elimination of translational controls and mislocalization. Hernández-Muñoz, I., Benet, M., Calero, M., Jiménez, M., Díaz, R., Pellicer, A. Cancer Res. (2003) [Pubmed]
  5. RAL GTPases are linchpin modulators of human tumour-cell proliferation and survival. Chien, Y., White, M.A. EMBO Rep. (2003) [Pubmed]
  6. Raloxifene enhances vertebral mechanical properties independent of bone density. Allen, M.R., Iwata, K., Sato, M., Burr, D.B. Bone (2006) [Pubmed]
  7. Docetaxel and gemcitabine activity in NSCLC cell lines and in primary cultures from human lung cancer. Zoli, W., Ricotti, L., Dal Susino, M., Barzanti, F., Frassineti, G.L., Folli, S., Tesei, A., Bacci, F., Amadori, D. Br. J. Cancer (1999) [Pubmed]
  8. Chromosomal localization and cDNA sequence of human ralB, a GTP binding protein. Hsieh, C.L., Swaroop, A., Francke, U. Somat. Cell Mol. Genet. (1990) [Pubmed]
  9. Cloning of the mouse desmoglein 3 gene (Dsg3): interspecies conservation within the cadherin superfamily. Ishikawa, H., Li, K., Tamai, K., Sawamura, D., Uitto, J. Exp. Dermatol. (2000) [Pubmed]
  10. Cardiovascular response to acute airway obstruction and hypoxia. Chapman, K.R., D'Urzo, A.D., Druck, M.N., Rebuck, A.S. Am. Rev. Respir. Dis. (1989) [Pubmed]
  11. Rosemary (Rosmarinus officinalis) diterpenes affect lipid polymorphism and fluidity in phospholipid membranes. Pérez-Fons, L., Aranda, F.J., Guillén, J., Villalaín, J., Micol, V. Arch. Biochem. Biophys. (2006) [Pubmed]
  12. Analyses of DNA adducts formed by ochratoxin A and aristolochic acid in patients with Chinese herbs nephropathy. Arlt, V.M., Pfohl-Leszkowicz, A., Cosyns, J., Schmeiser, H.H. Mutat. Res. (2001) [Pubmed]
  13. Respiratory alkalosis: no effect on blood lactate decline or exercise performance. Morrow, J.A., Fell, R.D., Gladden, L.B. European journal of applied physiology and occupational physiology. (1988) [Pubmed]
  14. A serine kinase associates with the RAL GTPase and phosphorylates RAL-interacting protein 1. Jilkina, O., Bhullar, R.P. Biochim. Biophys. Acta (2006) [Pubmed]
  15. Studies of all-trans-retinal as a photooxidizing agent. Harper, W.S., Gaillard, E.R. Photochem. Photobiol. (2001) [Pubmed]
  16. A photochemical study of (E,E,E,E)-2-[9-(2-hydroxyethyl)imino-3,7-dimethyl-1,3,5,7-decatrien-1-yl]- 1,3,3-trimethylcyclohexene, a derivative of all-trans-retinal and ethanolamine. Harper, W.S., Gaillard, E.R. Photochem. Photobiol. (2003) [Pubmed]
  17. Micronuclei and carcinogen DNA adducts as intermediate end points in nutrient intervention trial of precancerous lesions in the oral cavity. Prasad, M.P., Mukundan, M.A., Krishnaswamy, K. Eur. J. Cancer, B, Oral Oncol. (1995) [Pubmed]
  18. Carotid endarterectomy in patients with contralateral carotid occlusion: is the risk increased? McKittrick, J.E., MacLean, W.B., Lim, R.A. Annals of vascular surgery. (1989) [Pubmed]
  19. Immunochemical studies on fluctuation of phenylalanine ammonia-lyase activity in sweet potato in response to cut injury. Tanaka, Y., Uritani, I. J. Biochem. (1976) [Pubmed]
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