Identification of ROCK1 as an upstream activator of the JIP-3 to JNK signaling axis in response to UVB damage
Program in Molecular Medicine
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
Although apoptosis triggered by ultraviolet B (UVB)-mediated activation of the c-Jun N-terminal kinase (JNK) pathway is mediated by both intrinsic and extrinsic pathways, the mechanism of initiation of JNK activation remains obscure. Here, we report the characterization of the JNK-interacting protein 3 (JIP-3) scaffolding protein as an interacting partner of Rho-associated kinase 1 (ROCK1), as determined by tandem affinity protein purification. Upon UVB-induced stress in keratinocytes, ROCK1 was activated, bound to JIP-3, and activated the JNK pathway. Moreover, phosphorylation of JIP-3 by ROCK1 was crucial for the recruitment of JNK. Inhibition of the activity of ROCK1 in keratinocytes resulted in decreased activation of the JNK pathway and thus a reduction in apoptosis. ROCK1(+/-) mice exhibited decreased UVB-mediated activation of JNK and apoptosis relative to wild-type mice. Our findings present a new molecular mechanism by which ROCK1 functions as a UVB sensor that regulates apoptosis, an important event in the prevention of skin cancer.
DOI of Published Version
Sci Signal. 2008 Nov 25;1(47):ra14. doi: 10.1126/scisignal.1161938. Link to article on publisher's site
Ongusaha PP, Qi HH, Raj L, Kim Y, Aaronson SA, Davis RJ, Shi Y, Liao JK, Lee SW. (2008). Identification of ROCK1 as an upstream activator of the JIP-3 to JNK signaling axis in response to UVB damage. Davis Lab Publications. https://doi.org/10.1126/scisignal.1161938. Retrieved from https://escholarship.umassmed.edu/davis/71