Disease relevance of RGS6

• Here we provide new evidence that mild heat stress, proteasome-mediated proteotoxic stress, and HSF1 expression induces dramatic relocalization of RGS6 proteins from such sites to nucleoli [1].

High impact information on RGS6

• The expression of mRNA for RGS6 and Gbeta5 in human tissues overlaps [2].
• These data provide the first evidence that RGS proteins may be important modulators of cancer risk and validate RGS6 as a target for further study [3].
• In an epidemiologic study of 477 bladder cancer patients and 446 matched controls, three noncoding single-nucleotide polymorphisms (SNPs) in RGS2 and RGS6 were each associated with a statistically significant reduction in bladder cancer risk [3].
• We undertook a yeast two-hybrid screen for nuclear RGS6-binding proteins and here identify DMAP1 as an RGS6-interacting protein [4].
• This response was observed in COS-7 cells expressing various splice forms of RGS6, was not elicited by other forms of cellular stress and was observed in cells treated with various protein kinase inhibitors or co-expressing a dominant-negative kinase inactive SAPK [1].

Biological context of RGS6

• Here we report identification of 36 distinct transcripts of human RGS6 that arise by unusually complex processing of the RGS6 gene, which spans 630 kilobase pairs of genomic DNA in human chromosome 14 and is interrupted by 19 introns [5].
• Human RGS6 gene structure, complex alternative splicing, and role of N terminus and G protein gamma-subunit-like (GGL) domain in subcellular localization of RGS6 splice variants [5].
• The human regulator of G-protein signaling protein 6 gene (RGS6) maps between markers WI-5202 and D14S277 on chromosome 14q24.3 [6].

Anatomical context of RGS6

• These effects of RGS6 on microtubules and neuronal differentiation were observed only with RGS6 proteins with complete GGL domains [7].
• Our previous study documented unusual complexity in splicing of the human RGS6 gene, and we demonstrated localization of various RGS6 splice forms at sites other than the plasma membrane, including the cytoplasm and nucleus, where G proteins are not localized (Chatterjee, T. K., Liu, Z., and Fisher, R. A. (2003) J. Biol. Chem. 278, 30261-30271) [1].

Physical interactions of RGS6

• RGS6 splice variants with complete GGL domains interacted with G beta 5, irrespective of the type of N-terminal domain, while those lacking a complete GGL domain did not [5].

Regulatory relationships of RGS6

• RGS6 inhibited the transcriptional repressor activity of DMAP1 [4].
• RGS6 protein variants displayed subcellular distribution patterns ranging from an exclusive cytoplasmic to exclusive nuclear/nucleolar localization, and co-expression of G beta 5 promoted nuclear localization of RGS6 proteins [5].

Other interactions of RGS6

• Gbeta5 and DMAP1 did not compete for each other's interaction with RGS6 [4].
• The results suggest that there are interactions between RGS2, RGS6, and PDZ-RhoGEF and validate this family of proteins as key regulators of tumorigenesis [8].

Analytical, diagnostic and therapeutic context of RGS6

• Those of RGS6 and RGS9-2 proteins caused [D-Ala(2)]deltorphin II to produce a smoothened time-course curve-the peak effect blunted and analgesia extended during the declining phase [9].

References