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  • Identifying new proteoforms — structural variants of proteins — is frequently challenging, particularly on the proteome-wide scale. A new study leverages their differential thermal stabilities to identify proteoform functional groups by deep thermal proteome profiling.

    • Teagan L. Campbell
    • Bryon S. Drown
    News & Views
  • Applying thermal proteome profiling to acute B cell childhood leukemia cell lines combined with deep peptide fractionation and a graph-based clustering algorithm allows inference of functional proteoform groups and their association with drug response.

    • Nils Kurzawa
    • Isabelle Rose Leo
    • Rozbeh Jafari
    Article Open Access
  • A new review article details how new structural insight regarding modular polyketide synthases (PKSs) helps us better understand the organization of catalytic events within a PKS module. The plausible models discussed will likely influence future PKS engineering efforts.

    • Martin Grininger
    Review Article
  • Engineering synthetic tools that facilitate decision-making in mammalian cells could enable myriad biomedical applications. Researchers have now developed a new system of inducer-controlled transcription factors to facilitate synthetic decision-making (LOGIC) in human cells based on modular protein-fusion cascades.

    • Brian D. Huang
    • Ana S. De Pereda
    • Corey J. Wilson
    News & Views
  • Kim et al. used directed evolution methods to identify a high-fidelity SpCas9 variant, Sniper2L, which exhibits high general activity but maintains high specificity at a large number of target sites.

    • Young-hoon Kim
    • Nahye Kim
    • Hyongbum Henry Kim
    Article Open Access
  • We identified small molecules that rewire the transcriptional state of cancer cells by covalently targeting the RNA-binding protein NONO. These small molecules stabilize the interactions of NONO with its target mRNAs, thereby overriding the compensatory action of paralog proteins and revealing a pharmacological strategy for disrupting previously undruggable oncogenic pathways.

    Research Briefing
  • Integrated phenotypic screening and activity-based protein profiling identifies small molecules that decrease the expression of oncogenic transcription factors and suppress cancer cell growth by covalently targeting the RNA-binding protein NONO.

    • Stefan G. Kathman
    • Seong Joo Koo
    • Benjamin F. Cravatt