Disease relevance of RAB32

• Northern blots for Rab31 and Rab32 identified 4.4 kb and 1.35 kb mRNA species, respectively, in some human tissues and in human erythroleukemia (HEL) cells [1].
• HPP1 and RAB32 methylation was independent of MSI status and was observed in 4 of 59 and 0 of 64 nondysplastic mucosae, 20 of 38 and 1 of 25 dysplasias, and 28 of 61 and 20 of 60 carcinomas, respectively [2].
• Initial screening of six genes in 57 primary colon cancers detected the following gene with MSI-H cancer-specific hypermethylation: RAB32, a ras family member and A-kinase-anchoring protein, was methylated in 14 of 25 (56%) MSI-H cancers but in none of 32 non-MSI-H cancers or 23 normal colonic specimens [3].
• We sought to determine the prevalence of RAB32 hypermethylation in gastric and endometrial adenocarcinomas, the 2 other major tumor types in which MSI-H is common [4].
• Thirteen (27%) of 48 gastric cancers demonstrated evidence of RAB32 hypermethylation [4].

High impact information on RAB32

• Furthermore, HPP1 methylation occurs early, in 7% of nondysplastic and approximately half of dysplastic mucosae, whereas RAB32 methylation occurs at the transition to invasive growth, being rarer in dysplasias [2].
• This work identifies a key role for the Rab38/Rab32 subfamily of Rab proteins in the biogenesis of melanosomes and potentially other lysosome-related organelles [5].
• We report that cht Rab38(G19V) is inactive and that the nearly normal pigmentation in cht melanocytes results from functional compensation by the closely related Rab32 [5].
• Transient transfection of a GTP binding-deficient mutant of Rab32 promotes aberrant accumulation of mitochondria at the microtubule organizing center [6].
• RAB32 hypermethylation correlated with RAB32 mRNA down-regulation and with hMLH1 hypermethylation [3].

Biological context of RAB32

• RAB32 hypermethylation and microsatellite instability in gastric and endometrial adenocarcinomas [4].
• The recently described gene, RAB32, is a ras proto-oncogene family member that encodes an A-kinase-anchoring protein [4].
• RAB32 methylation was significantly associated with intestinal type histology and concomitant hMLH1 hypermethylation in gastric cancer [4].
• METHODS: A total of 124 IBDNs (81 cancers, 43 dysplasias) from 78 patients were studied for the frequency of MSI-H and hypermethylation of 3 target genes: MLH1 , HPP1 , and RAB-32 . Fifteen MSI-H IBDNs were characterized according to their profile of frameshift mutations in 28 mononucleotide repeats and compared with 46 sporadic MSI-H CRCs [2].

Anatomical context of RAB32

• Subcellular fractionation and immunofluorescent approaches indicate that Rab32 and a proportion of the cellular PKA pool are associated with mitochondria [6].

Associations of RAB32 with chemical compounds

• Binding of [(35)S]GTP[S] was optimal with 5 microm Mg(2+)(free) and was markedly inhibited by higher Mg(2+) concentrations in the case of GST-Rab31 but not GST-Rab32 [1].

Analytical, diagnostic and therapeutic context of RAB32

• Molecular cloning, bacterial expression and properties of Rab31 and Rab32 [1].

References