Year: 2018
Type: article
Abstract: Tankyrases (TNKS and TNKS2) are enzymes that catalyze poly-ADP-ribosylation (PARsylation) of their target proteins. Tankyrase-mediated PARsylation plays critical regulatory roles in cell signaling, particularly in the Wnt/β-catenin pathway. The sterile alpha motif (SAM) domain in tankyrases mediates their oligomerization, which is essential for tankyrase function. The oligomerization regulates the catalytic activity of tankyrases, but the underlying mechanism is unclear. Our analyses of crystal structures of the tankyrase catalytic domain suggest that formation of a head-to-head dimer regulates the catalytic activity. Our activity assays show that residues in the catalytic domain dimer interface are important for the PARsylation activity of tankyrases both in solution and cells. The dimer is weak and may only form in the context of the SAM domain-mediated oligomers of tankyrases, consistent with the dependence of the tankyrase activity on the SAM domain.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,110
Awards: Analyses of the Regulatory Mechanisms of Tankyrase and Its Role in Tumorigenesis, Mechanisms of Drug Action and Disposition, G147017651, A molecularly targeted anticancer therapeutic strategy premised upon attack of aberrant Wnt pathway responses, Targeting vismodegib-resistant tumors using BH3 mimetics, Chemical disruption of Wnt-mediated signal transduction, G5397080856, Targeting novel bromodomain protein in colorectal cancer, G7795998392
OpenAlex ID: W2883433077