Disease relevance of REPS2

• Identification of REPS2 as a putative modulator of NF-kappaB activity in prostate cancer cells [1].

High impact information on REPS2

• POB1 is a binding protein of RalBP1 and has the Eps15 homology (EH) domain [2].
• The EH domain of POB1 bound directly to Epsin and Eps15 [2].
• Deletion mutants of POB1 inhibited internalization of EGF and insulin [2].
• POB1 formed a complex with PAG2 in intact cells [3].
• The carboxyl-terminal region containing the proline-rich motifs of POB1 directly bound to the carboxyl-terminal region including the SH3 domain of PAG2 [3].

Chemical compound and disease context of REPS2

• The protein REPS2 is implicated in growth factor receptor-mediated endocytosis and signalling, and its expression is downregulated in androgen-independent prostate cancer cells [1].

Biological context of REPS2

• Hence, decreased expression of REPS2 might be a key factor, causing prostate cancer cells to become resistant to induction of apoptosis by androgen deprivation [1].
• During prostate cancer progression from androgen-dependent to androgen-independent growth, downregulation of REPS2 is accompanied by upregulation of NF-kappaB activity [1].
• Using crystal structure data from literature and experimental data from yeast and mammalian two-hybrid analysis, the results indicate that the NPF-motif in p65 acts as binding site for the EH domain in REPS2 [1].
• Overexpression, by transient transfection, of both forms of REPS2/POB1 in prostate cancer cell lines, induced apoptosis within 48 h [4].
• Co-expression with POB1 but not with POB1(PA) suppressed the inhibitory action of PAG2 on cell migration and paxillin localization [3].

Anatomical context of REPS2

• Ral and POB1 simultaneously interacted with RalBP1 in COS cells [5].
• The POB1 mRNA was expressed in cerebrum, cerebellum, lung, kidney, and testis [5].

Associations of REPS2 with chemical compounds

• 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 [6].
• 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 [5].

Physical interactions of REPS2

• Furthermore, POB1 bound to Grb2 but not to Nck or Crk [5].

Regulatory relationships of REPS2

• EGF signalling in prostate cancer cell lines is inhibited by a high expression level of the endocytosis protein REPS2 [7].
• POB1 over-expression inhibits RLIP76-mediated transport of glutathione-conjugates, drugs and promotes apoptosis [6].

Other interactions of REPS2

• Internalisation and signalling of EGF receptors was examined in different prostate cancer cell lines, in relation to the expression level of the endocytosis-related REPS2 gene [7].
• From these experiments, it is concluded that increased REPS2 expression negatively affects EGF receptor internalisation and subsequent signalling [7].
• Substitutions of Pro(423) and Pro(426) with Ala (POB1(PA)) impaired the binding of POB1 to PAG2 [3].
• These results suggest that phosphorylation of Epsin in mitotic phase inhibits receptor-mediated endocytosis by disassembly of its complex with POB1 and alpha-adaptin [8].
• In the calcium-bound state, the orientation of the fourth alpha-helix relative to the other helices of the POB1 EH domain is slightly different from that of calbindin, and much more different from those of calmodulin and troponin C, on the basis of their atomic coordinates [9].

References