A potential function of RLIP76 in the ovarian corpus luteum

Abstract

s Ral interacting protein of 76 kDa (RLIP76) is multifunctional protein localized and distributed in the plasma membrane, cytosol, and nucleus of the cell. In tumorigenesis, RLIP76 emerges as a common feature for the solid tumor growth. RLIP76 is ubiquitously expressed in various tissues including the ovary. Interestingly, the similar physiological events in obtaining an adequate supply of nutrient by gaining access to the host vascular system are required either for corpus luteum formation or tumor development. In addition, the identical angiogenesis modulators were found in neoplastic and normal ovaries. Our previous study involving RLIP76−/− mice implanted with melanoma or carcinoma cell conclusively demonstrated that RLIP76 is necessary for angiogenesis and neovascularization of primary solid tumors. RLIP76 plays an essential role in tumor angiogenesis through the regulation of pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF-1). In certain previous studies, those pro-angiogenic factors were found significantly to be upregulated during the corpus luteum formation. To that, the following review will discuss the likelihood of RLIP76 role in ovarian corpus luteum.

Haploinsufficiency Interactions of RALBP1 and TP53 in Carcinogenesis

“…Elevated 4HNE production from the high levels of oxidative stress imposed on cancer cells by their high metabolic rates renders them very dependent on this mechanism of metabolizing and disposing of 4HNE, as is evident from the dramatic and sustained regression of multiple histological types of cancer upon depletion or inhibition of RALBP1 in mouse models without any toxicity [ 10 , 11 , 55 ]. Our findings of inhibition of cancer growth in vitro and in vivo have been confirmed by several independent groups [ 44 , 48 , 49 , 56 , 57 , 58 ]. Evidence for the role of RALBP1 and other aldehyde-metabolizing enzymes in regulating the cancer-selective apoptotic effects of Ω-6 fatty acids and 4HNE in breast cancer is presented in one of the papers in this symposium.…”

The complexity of tumour angiogenesis based on recently described molecules

“…The ral-interacting protein of 76 kDa (RLIP76), known also as Ral-binding protein 1 (RalBP1), occurs in different compartments of the cell, including the cell membrane, intracellular fluid, and the nucleus [ 97 , 98 ]. The primary structure of RLIP76 might be divided into four main regions: the N-terminal region, the Rho-Gap region, the Ral binding region, and the C-terminal region [ 97 ]. Originally, RLIP76 was identified as a Ral GTPase effector protein, which links Ral to the Rho pathways [ 99 ].…”

“…Expression of RLIP76 was reported in a variety of human tissues, e.g. liver, heart, lung, kidney, ovary, and muscles [ 97 , 99 ]. RLIP76 is a stress-responsive multifunctional protein, involved in processes such as apoptosis, cell proliferation, differentiation, migration, and metabolite transport [ 97 , 98 , 100 ].…”

“…liver, heart, lung, kidney, ovary, and muscles [ 97 , 99 ]. RLIP76 is a stress-responsive multifunctional protein, involved in processes such as apoptosis, cell proliferation, differentiation, migration, and metabolite transport [ 97 , 98 , 100 ]. It consists of 2 ATP binding sites (in the N-terminal region and C-terminal regions) and is able to catalyse the transport and conjugation of glutathione and xenobiotics across the biological membranes, contributing to anti-apoptosis and multidrug resistance mechanisms in cancer cells [ 97 – 99 ].…”

“…RLIP76 is a stress-responsive multifunctional protein, involved in processes such as apoptosis, cell proliferation, differentiation, migration, and metabolite transport [ 97 , 98 , 100 ]. It consists of 2 ATP binding sites (in the N-terminal region and C-terminal regions) and is able to catalyse the transport and conjugation of glutathione and xenobiotics across the biological membranes, contributing to anti-apoptosis and multidrug resistance mechanisms in cancer cells [ 97 – 99 ]. RLIP76 overexpression was observed in numerous malignancies such as non-small cell lung carcinoma, colon carcinoma, prostate cancer, melanomas, gliomas, meningiomas, breast cancer, and pancreatic cancer [ 97 – 99 , 101 – 103 ].…”