Phosphorylation of PER2 at serine 662 regulates circadian timing, and its serine to glycine G (S662G) mutation causes familial advanced sleep phase syndrome. Liu et al. identify MARK2 as the physiological S662 kinase through biochemical purification. MARK2 stabilizes PER2 to regulate the circadian rhythm, and its loss in mice exhibits phase advancement and period shortening.

Zhang et al. use deep learning-based protein design to create isoform-specific Ras binders that selectively target the disordered C termini. These tools enable precise dissection of Ras isoform functions and uncover distinct Ras dependencies that emerge during RasG12C inhibitor resistance.

Yuan et al. identify TRIM28 as a key component of stress granules (SGs) using the lcFAX-MS approach established here and define TRIM28-mediated G3BP1/2 SUMOylation as a critical mechanism regulating SG dynamics. TRIM28’s role in regulating SGs, facilitated by lcFAX-MS, provides a promising framework for studying diverse LLPS events.

Loss of RNF43 leads to aberrant Wnt signaling, promoting aggressive cancers for which effective treatments are lacking. He et al. demonstrate that STT3A is critical for the survival of RNF43-deficient tumors, identifying it as a promising therapeutic target validated through both in vitro and in vivo studies.

Targeting the WDR5-MLL1 interaction offers a promising therapeutic strategy for leukemia. Zhang et al. developed Ac7, an EMBOW-derived peptide that binds WDR5 with nanomolar affinity, disrupts the WDR5-MLL1 interaction, and suppresses leukemia cell growth in vivo with relatively low toxicity.

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The field of microbiome research has experienced remarkable growth, leading to unprecedented discoveries of the molecular mechanisms that dictate host-microbiota interactions and their crucial roles i...

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