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 diseases1-3. 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 nucleus1,3 (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 radiation1,3-8 (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 Akt9-13 (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 disease1,3.

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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