AXIN Shapes Tankyrase ARChitecture
نویسندگان
چکیده
منابع مشابه
Crystal structure of a Tankyrase-Axin complex and its implications for Axin turnover and Tankyrase substrate recruitment.
Axin is a tumor suppressor and a key negative regulator of the Wnt/β-catenin signaling pathway. Axin turnover is controlled by its poly-ADP-ribosylation catalyzed by tankyrase (TNKS), which requires the direct interaction of Axin with TNKS. This interaction is thus an attractive drug target for treating cancers, brain injuries, and other diseases where β-catenin is involved. Here we report the ...
متن کاملTankyrase Inhibitors Stimulate the Ability of Tankyrases to Bind Axin and Drive Assembly of β-Catenin Degradation-Competent Axin Puncta
Activation of the wnt signaling pathway is a major cause of colon cancer development. Tankyrase inhibitors (TNKSi) have recently been developed to block the wnt pathway by increasing axin levels to promote degradation of the wnt-regulator β-catenin. TNKSi bind to the PARP (poly(ADP)ribose polymerase) catalytic region of tankyrases (TNKS), preventing the PARylation of TNKS and axin that normally...
متن کاملUbiquitin Ligase RNF146 Regulates Tankyrase and Axin to Promote Wnt Signaling
Canonical Wnt signaling is controlled intracellularly by the level of β-catenin protein, which is dependent on Axin scaffolding of a complex that phosphorylates β-catenin to target it for ubiquitylation and proteasomal degradation. This function of Axin is counteracted through relocalization of Axin protein to the Wnt receptor complex to allow for ligand-activated Wnt signaling. AXIN1 and AXIN2...
متن کاملLEF1 and B9L shield β-catenin from inactivation by Axin, desensitizing colorectal cancer cells to tankyrase inhibitors.
Hyperactive β-catenin drives colorectal cancer, yet inhibiting its activity remains a formidable challenge. Interest is mounting in tankyrase inhibitors (TNKSi), which destabilize β-catenin through stabilizing Axin. Here, we confirm that TNKSi inhibit Wnt-induced transcription, similarly to carnosate, which reduces the transcriptional activity of β-catenin by blocking its binding to BCL9, and a...
متن کاملLEF1 and B9L Shield b-Catenin from Inactivation by Axin, Desensitizing Colorectal Cancer Cells to Tankyrase Inhibitors
Hyperactive b-catenin drives colorectal cancer, yet inhibiting its activity remains a formidable challenge. Interest is mounting in tankyrase inhibitors (TNKSi), which destabilize b-catenin through stabilizing Axin. Here, we confirm that TNKSi inhibit Wnt-induced transcription, similarly to carnosate, which reduces the transcriptional activity of b-catenin by blocking its binding to BCL9, and a...
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ژورنال
عنوان ژورنال: Structure
سال: 2016
ISSN: 0969-2126
DOI: 10.1016/j.str.2016.09.003