October 2019 Newsletter: RhoB GTPase Tumor Supporter or Suppressor?

RhoB is a Rho-family GTPase that regulates essential physiological processes such as cell division, morphology, motility, adhesion, and intracellular transport, primarily through dynamic remodeling of the actin cytoskeleton, and whose expression and/or activity is pathologically dysfunctional in human diseases such as cancer and neurodegenerative diseases^1-3. Due to its unique C-terminal region and distinct post-translational modifications there, RhoB is localized not only to the plasma membrane (like other Rho GTPases), but also to endosomes, multivesicular bodies, and even the nucleus^1,3 (Fig. 1). Like other Rho-family GTPases, RhoB functions as a binary switch in signaling cascades, cycling between a GDP-bound, inactive state and a GTP-bound, active state. The GTP/GDP cycling is controlled by guanine nucleotide exchange factors (GEFs; activation by exchanging GDP for GTP) and GTPase-activating proteins (GAPs; inactivation by GTP hydrolysis)^1-3.

RhoB expression and/or activity is regulated by a variety of physiological stimuli. Normally expressed at low levels under steady state conditions, RhoB expression and/or activity is rapidly up-regulated by hypoxia, growth factors, inflammatory cytokines, and stress stimuli including UV radiation^1,3-8 (Fig. 1). Upon activation, RhoB regulates cellular responses to UV-induced DNA damage, apoptosis, cell cycle progression, and cell migration (and invasion in the case of cancer cells)^1,3. RhoB’s distinctive subcellular localization to membrane vesicles enables RhoB-mediated regulation of intracellular transport. Endosome-localized RhoB regulates the trafficking (and thereby function) of receptor tyrosine kinase and cytokine receptor-mediated signaling cascades (e.g., EGFR, CXCR2, TNFR) and the activities of kinases such as Src and Akt^9-13 (Fig. 1). As a result, RhoB is able to regulate a wide range of essential signaling cascades involved in cellular development, proliferation, survival, and apoptosis – all pathways important in human physiology and disease^1,3.

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 Also included in this newsletter:

• Tubulin and Actin Live Cell Reagents, G-LISA Activation Assay Kits, Tubulin Kits, Actin Biochem Kits

• Related Publications