Rho GTPase-activating protein 36 (ARHGAP36)

Rho GTPase-activating protein 36 (ARHGAP36) is an atypical member of the Rho GTPase-activating protein family, notable for its multidomain structure and noncanonical enzymatic activity. Unlike classical Rho GAPs, ARHGAP36 lacks the "arginine finger" necessary for catalytic Rho GTPase activity but acts as a potent signal transduction mediator in neural development and various cancers. It promotes Hedgehog pathway activation independently of the Smoothened receptor by inhibiting protein kinase A (PKA) and activating Gli transcription factors[1][2][3][4][5]. ARHGAP36 regulates cell fate through PKA degradation (via pseudosubstrate inhibition and ubiquitin-mediated lysosomal proteolysis), leading to enhanced Gli-driven transcription and proliferation. Overexpression of ARHGAP36 is implicated in tumor initiation, progression, and drug resistance, particularly in medulloblastoma. The protein also modulates cellular trafficking and interacts with various regulatory partners in the ciliary compartment, highlighting its essential role in developmental signaling and cancer biology[1][2][5].

Other names

ARHGAP36FLJ30058Rho GTPase activating protein 36

No approved drugs; mechanisms for potential targeting could involve inhibition of ARHGAP36-driven Gli activation, Hedgehog pathway modulation, or PKA pathway interaction