Disease relevance of RAC3

• The RAC3 gene was mapped to chromosome 17q23-25, a region frequently deleted in breast cancer [1].
• Thus, functional analysis of Rac1 and Rac3 using RNA interference reveals a critical role for these GTPases in the invasive behavior of glioma and breast carcinoma cells [2].
• Moreover, our data suggest that interference with Rac3 activity, for example, by using geranyl-geranyltransferase inhibitors, may provide a positive clinical benefit for patients with Ph-positive acute lymphoblastic leukemia [3].

High impact information on RAC3

• Endogenous, hyperactive Rac3 controls proliferation of breast cancer cells by a p21-activated kinase-dependent pathway [4].
• Only the Rac3-Pak pathway was critical for DNA synthesis, independently of JNK [4].
• In this paper, we show that endogenous, hyperactive Rac3 is present in highly proliferative human breast cancer-derived cell lines and tumor tissues [4].
• Rac3 activity results from both its distinct subcellular localization at the membrane and altered regulatory factors affecting the guanine nucleotide state of Rac3 [4].
• We report here the cloning and characterization of receptor-associated coactivator 3 (RAC3), a human transcriptional coactivator for steroid/nuclear receptors [5].

Biological context of RAC3

• We previously mapped RAC3 to chromosome band 17q23--> q25, a region that contains a number of candidate tumour suppressor genes [6].
• Interestingly, whereas depletion of Rac3 strongly inhibits SNB19 cell invasion, it does not affect lamellipodia formation and has only minor effects on cell migration and proliferation [2].
• Here we show that Rac1 and Rac3 are very closely related concerning their biochemical properties, such as effector interaction, nucleotide binding and hydrolysis [7].
• Expression of a dominant active Rac1 or a dominant active Rac3 resulted in a more invasive and motile phenotype [8].
• This shows Rac3 function is dispensable for embryonic development [3].

Anatomical context of RAC3

• Rac3 protein levels are not affected by organization of the actin cytoskeleton but remarkably, are serum-inducible [1].
• Immunocytochemistry showed that NRBP and activated Rac3 co-localized to endomembranes and at the cell periphery in lamellipodia [9].

Associations of RAC3 with chemical compounds

• A role for Rac3 in integrin-mediated adhesion and spreading has not been defined [10].

Physical interactions of RAC3

• The small GTPase Rac3 interacts with the integrin-binding protein CIB and promotes integrin alpha(IIb)beta(3)-mediated adhesion and spreading [10].

Co-localisations of RAC3

• Also, CIB co-localized with active Rac3 to the periphery of cells adhering to fibrinogen [10].

Other interactions of RAC3

• Rac3 differs from Rac1/2 at its carboxyl-terminal end, a domain associated with subcellular localization and binding to specific cellular regulators [1].
• Structure and chromosomal assignment to 22q12 and 17qter of the ras-related Rac2 and Rac3 human genes [11].
• Binding of V12Rac3 to CIB was mediated by the C-terminal end of Rac3 and by Rac3 membrane localization [10].
• The Rac1-opposing function of Rac3 is not mediated by or dependent on components of the RhoA signaling pathway [12].
• Our data suggest that Rac3 and Rac1 oppose each other's function by differently modulating GIT1 signaling [13].

Analytical, diagnostic and therapeutic context of RAC3

• To investigate if Rac3 contributes to normal or malignant cell function, we generated rac3 null mutants through gene targeting [3].

References