Publications by authors named "M L Maitland"
The Pro/N-degron recognizing C-terminal to LisH (CTLH) complex is an E3 ligase of emerging interest in the developmental biology field and for targeted protein degradation (TPD) modalities. The human CTLH complex forms distinct supramolecular ring-shaped structures dependent on the multimerization of WDR26 or muskelin β-propeller proteins. Here, we find that, in HeLa cells, CTLH complex E3 ligase activity is dictated by an interplay between WDR26 and muskelin in tandem with muskelin autoregulation.
View Article and Find Full Text PDFTargeted protein degradation (TPD) is an emerging therapeutic strategy that would benefit from new chemical entities with which to recruit a wider variety of ubiquitin E3 ligases to target proteins for proteasomal degradation. Here we describe a TPD strategy involving the recruitment of FBXO22 to induce degradation of the histone methyltransferase and oncogene NSD2. UNC8732 facilitates FBXO22-mediated degradation of NSD2 in acute lymphoblastic leukemia cells harboring the NSD2 gain-of-function mutation p.
View Article and Find Full Text PDFArticle Synopsis
- The CTLH complex, involved in recognizing specific protein substrates via GID4, has unclear functions and targets in humans.
- Researchers introduced PFI-7, a chemical probe that inhibits GID4's ability to bind Pro/N-degrons, which helps identify proteins GID4 interacts with and regulates.
- Their findings reveal GID4's role in regulating levels of nucleolar proteins and metabolic enzymes, suggesting both degradative and nondegradative actions, and highlighting PFI-7's potential for future research on protein degradation strategies.
Background: Protein arginine methyltransferase 5 (PRMT5) methylates multiple substrates dysregulated in cancer, including spliceosome machinery components. PF-06939999 is a selective small-molecule PRMT5 inhibitor.
Patients And Methods: This phase I dose-escalation and -expansion trial (NCT03854227) enrolled patients with selected solid tumors.