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RalA-binding protein 1

Definition:

Multifunctional protein that functions as a downstream effector of RALA and RALB. As a GTPase-activating protein/GAP can inactivate CDC42 and RAC1 by stimulating their GTPase activity. As part of the Ral signaling pathway, may also regulate ligand-dependent EGF and insulin receptors-mediated endocytosis. During mitosis, may act as a scaffold protein in the phosphorylation of EPSIN/EPN1 by the mitotic kinase cyclin B-CDK1, preventing endocytosis during that phase of the cell cycle. During mitosis, also controls mitochondrial fission as an effector of RALA. Recruited to mitochondrion by RALA, acts as a scaffold to foster the mitotic kinase cyclin B-CDK1-mediated phosphorylation and activation of DNM1L.; Could also function as a primary ATP-dependent active transporter for glutathione conjugates of electrophiles. May also actively catalyze the efflux of a wide range of substrates including xenobiotics like doxorubicin (DOX) contributing to cell multidrug resistance.

References:

[1]. David F Kashatus, et al. RALA and RALBP1 regulate mitochondrial fission at mitosis. Nat Cell Biol. 2011 Aug 7;13(9):1108-15. [Content Brief]

[2]. S Awasthi, et al. Novel function of human RLIP76: ATP-dependent transport of glutathione conjugates and doxorubicin. Biochemistry. 2000 Aug 8;39(31):9327-34. [Content Brief]

[3]. R Sharma, et al. RLIP76 is the major ATP-dependent transporter of glutathione-conjugates and doxorubicin in human erythrocytes. Arch Biochem Biophys. 2001 Jul 15;391(2):171-9. [Content Brief]

[4]. V Jullien-Flores, et al. Bridging Ral GTPase to Rho pathways. RLIP76, a Ral effector with CDC42/Rac GTPase-activating protein activity. J Biol Chem. 1995 Sep 22;270(38):22473-7. [Content Brief]

[5]. S Awasthi, et al. ATP-Dependent human erythrocyte glutathione-conjugate transporter. II. Functional reconstitution of transport activity. Biochemistry. 1998 Apr 14;37(15):5239-48. [Content Brief]

[6]. V Jullien-Flores, et al. RLIP76, an effector of the GTPase Ral, interacts with the AP2 complex: involvement of the Ral pathway in receptor endocytosis. J Cell Sci. 2000 Aug;113 ( Pt 16):2837-44. [Content Brief]

[7]. Carine Rossé, et al. RLIP, an effector of the Ral GTPases, is a platform for Cdk1 to phosphorylate epsin during the switch off of endocytosis in mitosis. J Biol Chem. 2003 Aug 15;278(33):30597-604. [Content Brief]

[8]. S Awasthi, et al. Functional reassembly of ATP-dependent xenobiotic transport by the N- and C-terminal domains of RLIP76 and identification of ATP binding sequences. Biochemistry. 2001 Apr 3;40(13):4159-68. [Content Brief]

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