RalA-binding protein 1 (RalBP1, Ral-interacting protein 1, 76 kD Ral-interacting protein, dinitrophenyl S-glutathione ATPase, DNP-SG ATPase, RALBP1, RLIP1, RLIP76)
Jump to navigation
Jump to search
Function
- activates hydrolysis of GTP bound to RAC1 & CDC42, but not RALA
- mediates ATP-dependent transport of S-(2,4-dinitrophenyl)- glutathione (DNP-SG) & doxorubicin (DOX)
- major ATP-dependent transporter of glutathione conjugates of electrophiles (GS-E) & DOX in erythrocytes
- facilitates transport of glutathione conjugates & xenobiotics
- role in multidrug resistance phenomenon (putative)
- role as a scaffold protein that brings together proteins forming an endocytotic complex during interphase
- role with CDK1 to switch off endocytosis
- interacts with the GTP-bound form of RALA, RALB, CDC42, RAC1
- interacts with REPS1 & REPS2 (does not affect Ral-binding)
- interacts with DAB2IP
- interacts with catalytically active CCNB1 & CDK1 during mitosis
- interacts with EPN1, NUMB & TFAP2A during interphase & mitosis
Structure
- contains 1 Rho-GAP domain
Compartment
membrane, peripheral membrane
Expression
- expressed ubiquitously but at low levels
- strong expression in erythrocytes
Pathology
- autoantibodies to RLIP76 may play a role in vascular disease[19]
Comparative biology
- knockout of RLIP in mice may confer immunity to both multiple cancers & the metabolic syndrome
- the suggestion is made that RLIP76 inhibition may play a role in the benefits of calorie restriction[21]
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/Q15311.html
- ↑ Awasthi S, Singhal SS, Yadav S, Singhal J et a; A central role of RLIP76 in regulation of glycemic control. Diabetes. 2010 Mar;59(3):714-25 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20007934
- ↑ Singhal SS, Yadav S, Roth C, Singhal J. RLIP76: A novel glutathione-conjugate and multi-drug transporter. Biochem Pharmacol. 2009 Mar 1;77(5):761-9 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18983828
- ↑ Singhal J, Singhal SS, Yadav S et al RLIP76 in defense of radiation poisoning. Int J Radiat Oncol Biol Phys. 2008 Oct 1;72(2):553-61 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18793957
- ↑ Awasthi S, Singhal SS, Awasthi YC et al RLIP76 and Cancer. Clin Cancer Res. 2008 Jul 15;14(14):4372-7 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18628450
- ↑ Awasthi S, Singhal SS, Yadav S et al RLIP76 is a major determinant of radiation sensitivity. Cancer Res. 2005 Jul 15;65(14):6022-8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16024601.
- ↑ Singhal SS, Figarola J, Singhal J et al RLIP76 knockdown attenuates obesity due to high-fat diet. J Biol Chem. 2013 Jul 2 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23821548
- ↑ Sehrawat A, Yadav S, Awasthi YC et al P300 regulates the human RLIP76 promoter activity and gene expression. Biochem Pharmacol. 2013 Apr 15;85(8):1203-11 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23419874
- ↑ Lee S, Wurtzel JG, Singhal SS, Awasthi S, Goldfinger LE RALBP1/RLIP76 depletion in mice suppresses tumor growth by inhibiting tumor neovascularization. Cancer Res. 2012 Oct 15;72(20):5165-73 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22902412
- ↑ Leake K, Singhal J, Nagaprashantha LD, Awasthi S, Singhal SS. RLIP76 regulates PI3K/Akt signaling and chemo-radiotherapy resistance in pancreatic cancer. PLoS One. 2012;7(4):e34582 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22509328
- ↑ Singhal J, Nagaprashantha L, Vatsyayan R et al RLIP76, a glutathione-conjugate transporter, plays a major role in the pathogenesis of metabolic syndrome. PLoS One. 2011;6(9):e24688 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21931813
- ↑ Kashatus DF, Lim KH, Brady DC et al RALA and RALBP1 regulate mitochondrial fission at mitosis. Nat Cell Biol. 2011 Aug 7;13(9):1108-15 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21822277
- ↑ Vatsyayan R, Lelsani PC, Awasthi S, Singhal SS. RLIP76: a versatile transporter and an emerging target for cancer therapy. Biochem Pharmacol. 2010 Jun 15;79(12):1699-705 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20097178
- ↑ Vatsyayan R, Chaudhary P, Lelsani PC et al Role of RLIP76 in doxorubicin resistance in lung cancer Int J Oncol. 2009 Jun;34(6):1505-11 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19424567
- ↑ Singhal SS, Singhal J, Yadav S et al RLIP76: a target for kidney cancer therapy. Cancer Res. 2009 May 15;69(10):4244-51 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19417134
- ↑ Singhal SS, Yadav S, Vatsyayan R et al Increased expression of cdc2 inhibits transport function of RLIP76 and promotes apoptosis. Cancer Lett. 2009 Oct 8;283(2):152-8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19375851
- ↑ Singhal SS, Sehrawat A, Mehta A, Sahu M, Awasthi S. Functional reconstitution of RLIP76 catalyzing ATP-dependent transport of glutathione-conjugates. Int J Oncol. 2009 Jan;34(1):191-9 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19082490
- ↑ Singhal SS, Roth C, Leake K, Singhal J, Yadav S, Awasthi S. Regression of prostate cancer xenografts by RLIP76 depletion. Biochem Pharmacol. 2009 Mar 15;77(6):1074-83 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19073149
- ↑ 19.0 19.1 Margutti P, Matarrese P, Conti F et al Autoantibodies to the C-terminal subunit of RLIP76 induce oxidative stress and endothelial cell apoptosis in immune- mediated vascular diseases and atherosclerosis. Blood. 2008 May 1;111(9):4559-70 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17993611
- ↑ Singhal SS, Figarola J, Singhal J et al RLIP76 Knockdown Attenuates Obesity Due to High-Fat Diet. J Biol. Chem. July 2, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23821548 <Internet> http://www.jbc.org/content/early/2013/07/02/jbc.M113.480194.long
- ↑ 21.0 21.1 Darwin M GRG posting: July 17, 2012 http://lists.ucla.edu/cgi-bin/mailman/listinfo/grg