Three New Preprints!

1.          Intracellular Protein Editing to Enable Incorporation of Non-Canonical Residues into Endogenous Proteins, J.N. Beyer, Y.V. Serebrenik, K. Toy, M.A. Najar, N.R. Raniszewski, O. Shalem* and G.M. Burslem*

             Biorxiv: 10.1101/2024.07.08.602493

The first describes our intra-cellular protein editing approach to site specifically incorporate a non-canonical residue in a cell, enabling pulldowns without an antibody and the use of a small molecule fluorophore to image an endogenous protein!

2.          The Interplay of Acetylation and Ubiquitination Controls PRMT1 Homeostasis, M.A. Najar, J.N. Beyer, C.M. Crawford, and G.M. Burslem

Biorxiv: 10.1101/2024.06.18.599616

The second is the first of several (watch this space) papers on the roles of lysine acetylation in protein homeostasis. We show that once acetylated, PRMT1 is recognized by the E3 ligase FBXL17, resulting in it’s ubiquitination and degradation. We applied mammalian genetic code expansion to site specifically incorporate authentic acetyl-lysine into PRMT1 to confirm our findings.

3.          A selective S-acyltransferase inhibitor suppresses tumor growth J.Y. Lee, S. Dilones, T. Maujean, M. Asad, M.A. Najar, N. Auslander. D.C. Brady, G.M. Burslem* and E.S. Witze*

             Biorxiv: 10.1101/2024.06.18.599616

The third reports on the discovery and optimization of the first drug like inhibitor of DHHC palmitoyl transferases. Our lead compound fully phenocopies genetic ablation of DHHC20, is orally available and improves survival in murine KRas mutant lung cancer xenografts!