Our latest work, led by PhD student Drew Grant, describes a novel mode of substrate selection by the CTLH E3 ubiquitin ligase complex. CTLH is an intriguing multi-subunit E3 ligase whose substrate repertoire remains poorly understood. By performing comparative stability profiling with two human 'ORFeome' expression libraries differing in their C-terminal sequences, Drew identified ZMYND19 as a substrate harbouring a -PER* C-terminal degron targeted by the Muskelin subunit of CTLH. Further genetic and proteomic screens identified the uncharacterised protein AAMP as an additional substrate of this pathway; Drew's work shows that AAMP is the orthologue of yeast Sqt1 and functions similarly as a chaperone for the ribosomal protein uL16/RPL10.

The full preprint is now available on bioRxiv at https://www.biorxiv.org/content/10.64898/2026.01.14.698769v1.

We are very grateful for assistance from our collaborators in the Warren and Weekes Labs (Cambridge Institute for Medical Research), the Elledge Lab (Harvard Medical School) and the Tchasovnikarova Lab (Gurdon Institute).