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Gene Review

RALBP1  -  ralA binding protein 1

Homo sapiens

Synonyms: 76 kDa Ral-interacting protein, DNP-SG ATPase, Dinitrophenyl S-glutathione ATPase, RIP, RIP1, ...
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Disease relevance of RALBP1


Psychiatry related information on RALBP1

  • In this article, we discuss the significance of transport functions of RLIP76 highlighting its role in the defense mechanisms against oxidative injury, and modulation of signaling mechanisms [6].

High impact information on RALBP1


Chemical compound and disease context of RALBP1


Biological context of RALBP1


Anatomical context of RALBP1


Associations of RALBP1 with chemical compounds

  • RLIP76 (RALBP1) is a Ral-binding nucleotidase which functions as an energy-dependent transporter for glutathione (GSH)-conjugates as well as structurally unrelated xenobiotics [13].
  • Both doxorubicin and a model GSH-conjugate, dinitrophenyl-S-glutathione (DNP-SG), transport were inhibited by POB1 in a concentration-dependent manner but not by POB1(1-512), lacking RLIP76-binding site [13].
  • A key step in the mercapturic acid pathway, efflux of the glutathione-electrophile conjugate has recently been shown to be catalyzed largely by the stress-responsive protein RLIP76, a splice variant peptide endowed by the human gene RALBP1 [22].
  • Depletion of Triad3A by small interference RNA treatment inhibited geldanamycin-activated ubiquitination and proteolytic degradation of RIP1 [23].
  • These results suggest that RalBP1 makes a complex with POB1 and that this complex may provide a link between tyrosine kinase, Src homology 3 (SH3)-containing protein, and Ral [18].

Physical interactions of RALBP1


Enzymatic interactions of RALBP1


Regulatory relationships of RALBP1

  • These results reveal the biochemical mechanism underlying the essential signaling function of NEMO and provide direct evidence that signal-induced site-specific ubiquitination of RIP1 is required for IKK activation [7].
  • These results suggest that RLIP76 is the major LTC(4) transporter in cancer cells and that its transport activity is regulated by PKC-alpha-mediated phosphorylation [25].
  • Ral-binding protein 1 (RalBP1) is a putative effector protein of Ral and possesses the GTPase-activating activity for Rac1 and CDC42 [20].
  • Stress-pre-conditioned cells with induced hGST5.8 and RLIP76 acquired resistance to 4-HNE and H2O2-mediated apoptosis by suppressing a sustained activation of c-Jun N-terminal kinase and caspase 3 [27].
  • The antibodies raised against human erythrocyte Dnp-SG ATPase cross-reacted with the bovine lens epithelium Dnp-SG ATPase which was identified by Western blot as a band corresponding to an approximate M(r) value of 80,000 Da [28].

Other interactions of RALBP1

  • However, internalization of transferrin was unaffected by Ral, RalBP1, POB1 and their mutants [16].
  • Stimulation of tumor necrosis factor receptor 1 (TNFR1) can initiate several cellular responses, including apoptosis, which relies on caspases, necrotic cell death, which depends on receptor-interacting protein kinase 1 (RIP1), and NF-kappaB activation, which induces survival and inflammatory responses [17].
  • RLIP76, an effector of the GTPase Ral, interacts with the AP2 complex: involvement of the Ral pathway in receptor endocytosis [24].
  • We demonstrate RLIP76 reconstituted in artificial liposomes can catalyze ATP-dependent transport of LTC(4), which can be modulated by PKC-alpha [25].
  • We examined the roles of the post-translational modifications of Ral and Rac1 for the action of RalBP1 [20].

Analytical, diagnostic and therapeutic context of RALBP1


  1. Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Singhal, S.S., Singhal, J., Nair, M.P., Lacko, A.G., Awasthi, Y.C., Awasthi, S. Int. J. Oncol. (2007) [Pubmed]
  2. RALBP1/RLIP76 mediates multidrug resistance. Drake, K.J., Singhal, J., Yadav, S., Nadkar, A., Pungaliya, C., Singhal, S.S., Awasthi, S. Int. J. Oncol. (2007) [Pubmed]
  3. Novel function of human RLIP76: ATP-dependent transport of glutathione conjugates and doxorubicin. Awasthi, S., Cheng, J., Singhal, S.S., Saini, M.K., Pandya, U., Pikula, S., Bandorowicz-Pikula, J., Singh, S.V., Zimniak, P., Awasthi, Y.C. Biochemistry (2000) [Pubmed]
  4. The role of PKCalpha and RLIP76 in transport-mediated doxorubicin-resistance in lung cancer. Singhal, S.S., Yadav, S., Singhal, J., Drake, K., Awasthi, Y.C., Awasthi, S. FEBS Lett. (2005) [Pubmed]
  5. Hsf-1 and POB1 induce drug sensitivity and apoptosis by inhibiting Ralbp1. Singhal, S.S., Yadav, S., Drake, K., Singhal, J., Awasthi, S. J. Biol. Chem. (2008) [Pubmed]
  6. Transport functions and physiological significance of 76 kDa Ral-binding GTPase activating protein (RLIP76). Awasthi, S., Sharma, R., Yang, Y., Singhal, S.S., Pikula, S., Bandorowicz-Pikula, J., Singh, S.V., Zimniak, P., Awasthi, Y.C. Acta Biochim. Pol. (2002) [Pubmed]
  7. Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Ea, C.K., Deng, L., Xia, Z.P., Pineda, G., Chen, Z.J. Mol. Cell (2006) [Pubmed]
  8. Adenosine triphosphate-dependent transport of doxorubicin, daunomycin, and vinblastine in human tissues by a mechanism distinct from the P-glycoprotein. Awasthi, S., Singhal, S.S., Srivastava, S.K., Zimniak, P., Bajpai, K.K., Saxena, M., Sharma, R., Ziller, S.A., Frenkel, E.P., Singh, S.V. J. Clin. Invest. (1994) [Pubmed]
  9. RLIP76, a novel transporter catalyzing ATP-dependent efflux of xenobiotics. Awasthi, S., Sharma, R., Singhal, S.S., Zimniak, P., Awasthi, Y.C. Drug Metab. Dispos. (2002) [Pubmed]
  10. RLIP76, a non-ABC transporter, and drug resistance in epilepsy. Awasthi, S., Hallene, K.L., Fazio, V., Singhal, S.S., Cucullo, L., Awasthi, Y.C., Dini, G., Janigro, D. BMC neuroscience [electronic resource]. (2005) [Pubmed]
  11. Protein sequence requirements for function of the human T-cell leukemia virus type 1 Rex nuclear export signal delineated by a novel in vivo randomization-selection assay. Bogerd, H.P., Fridell, R.A., Benson, R.E., Hua, J., Cullen, B.R. Mol. Cell. Biol. (1996) [Pubmed]
  12. Identification of membrane-anchoring domains of RLIP76 using deletion mutant analyses. Yadav, S., Singhal, S.S., Singhal, J., Wickramarachchi, D., Knutson, E., Albrecht, T.B., Awasthi, Y.C., Awasthi, S. Biochemistry (2004) [Pubmed]
  13. POB1 over-expression inhibits RLIP76-mediated transport of glutathione-conjugates, drugs and promotes apoptosis. Yadav, S., Zajac, E., Singhal, S.S., Singhal, J., Drake, K., Awasthi, Y.C., Awasthi, S. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  14. RLIP76 is a major determinant of radiation sensitivity. Awasthi, S., Singhal, S.S., Yadav, S., Singhal, J., Drake, K., Nadkar, A., Zajac, E., Wickramarachchi, D., Rowe, N., Yacoub, A., Boor, P., Dwivedi, S., Dent, P., Jarman, W.E., John, B., Awasthi, Y.C. Cancer Res. (2005) [Pubmed]
  15. Transport of glutathione conjugates and chemotherapeutic drugs by RLIP76 (RALBP1): a novel link between G-protein and tyrosine kinase signaling and drug resistance. Awasthi, S., Singhal, S.S., Sharma, R., Zimniak, P., Awasthi, Y.C. Int. J. Cancer (2003) [Pubmed]
  16. Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors. Nakashima, S., Morinaka, K., Koyama, S., Ikeda, M., Kishida, M., Okawa, K., Iwamatsu, A., Kishida, S., Kikuchi, A. EMBO J. (1999) [Pubmed]
  17. Competitive control of independent programs of tumor necrosis factor receptor-induced cell death by TRADD and RIP1. Zheng, L., Bidere, N., Staudt, D., Cubre, A., Orenstein, J., Chan, F.K., Lenardo, M. Mol. Cell. Biol. (2006) [Pubmed]
  18. Identification and characterization of a novel protein interacting with Ral-binding protein 1, a putative effector protein of Ral. Ikeda, M., Ishida, O., Hinoi, T., Kishida, S., Kikuchi, A. J. Biol. Chem. (1998) [Pubmed]
  19. RLIP, an effector of the Ral GTPases, is a platform for Cdk1 to phosphorylate epsin during the switch off of endocytosis in mitosis. Rossé, C., L'Hoste, S., Offner, N., Picard, A., Camonis, J. J. Biol. Chem. (2003) [Pubmed]
  20. The post-translational modifications of Ral and Rac1 are important for the action of Ral-binding protein 1, a putative effector protein of Ral. Matsubara, K., Hinoi, T., Koyama, S., Kikuchi, A. FEBS Lett. (1997) [Pubmed]
  21. RLIP76 is the major ATP-dependent transporter of glutathione-conjugates and doxorubicin in human erythrocytes. Sharma, R., Singhal, S.S., Cheng, J., Yang, Y., Sharma, A., Zimniak, P., Awasthi, S., Awasthi, Y.C. Arch. Biochem. Biophys. (2001) [Pubmed]
  22. Linking stress-signaling, glutathione metabolism, signaling pathways and xenobiotic transporters. Yadav, S., Zajac, E., Singhal, S.S., Awasthi, S. Cancer Metastasis Rev. (2007) [Pubmed]
  23. Triad3A Regulates Ubiquitination and Proteasomal Degradation of RIP1 following Disruption of Hsp90 Binding. Fearns, C., Pan, Q., Mathison, J.C., Chuang, T.H. J. Biol. Chem. (2006) [Pubmed]
  24. RLIP76, an effector of the GTPase Ral, interacts with the AP2 complex: involvement of the Ral pathway in receptor endocytosis. Jullien-Flores, V., Mahé, Y., Mirey, G., Leprince, C., Meunier-Bisceuil, B., Sorkin, A., Camonis, J.H. J. Cell. Sci. (2000) [Pubmed]
  25. RLIP76 (RALBP1)-mediated transport of leukotriene C4 (LTC4) in cancer cells: implications in drug resistance. Sharma, R., Singhal, S.S., Wickramarachchi, D., Awasthi, Y.C., Awasthi, S. Int. J. Cancer (2004) [Pubmed]
  26. A serine kinase associates with the RAL GTPase and phosphorylates RAL-interacting protein 1. Jilkina, O., Bhullar, R.P. Biochim. Biophys. Acta (2006) [Pubmed]
  27. Accelerated metabolism and exclusion of 4-hydroxynonenal through induction of RLIP76 and hGST5.8 is an early adaptive response of cells to heat and oxidative stress. Cheng, J.Z., Sharma, R., Yang, Y., Singhal, S.S., Sharma, A., Saini, M.K., Singh, S.V., Zimniak, P., Awasthi, S., Awasthi, Y.C. J. Biol. Chem. (2001) [Pubmed]
  28. Low and high Km forms of dinitrophenylglutathione-stimulated ATPase in bovine lens. Kumari, K., Ansari, N.H., Saxena, M., Awasthi, Y.C., Srivastava, S.K. Exp. Eye Res. (1993) [Pubmed]
  29. Role of RLIP76 in lung cancer doxorubicin resistance: III. Anti-RLIP76 antibodies trigger apoptosis in lung cancer cells and synergistically increase doxorubicin cytotoxicity. Awasthi, S., Singhal, S.S., Singhal, J., Yang, Y., Zimniak, P., Awasthi, Y.C. Int. J. Oncol. (2003) [Pubmed]
  30. Role of RLIP76 in lung cancer doxorubicin resistance: I. The ATPase activity of RLIP76 correlates with doxorubicin and 4-hydroxynonenal resistance in lung cancer cells. Singhal, S.S., Singhal, J., Sharma, R., Singh, S.V., Zimniak, P., Awasthi, Y.C., Awasthi, S. Int. J. Oncol. (2003) [Pubmed]
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