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GAPVD1 regulates CSNK1D-dependent PER2 FASP phosphorylation

The mammalian circadian clock relies on precisely timed transcriptional and post-translational events to generate ~24-hour rhythms. A key post-translational mechanism is phosphorylation of PER2 by CSNK1D, governed by a phosphoswitch that integrates stabilizing and destabilizing phosphorylation marks at the FASP and Degron sites to control PER2 stability and circadian period. Here, a novel role for the PER complex protein GAPVD1 in regulating CSNK1D-mediated FASP site phosphorylation is revealed.

bioRxiv 10d ago

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer

Abstract BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1,2,3.

Nature 22h ago

Tet Trim-Away: A conditional rapid protein degradation system for Tetrahymena thermophila

Tetrahymena thermophila is a ciliated protist that has played pivotal roles in biological discovery. Functional studies of Tetrahymena proteins have largely relied on gene knockouts. Because protein depletion upon knockout typically spans multiple cell cycles, compensatory mechanisms can confound phenotypic interpretation.

bioRxiv 6d ago