Orphan protein quality control maintains the embryonic stem cell state
In the course of gene expression, multisubunit transcription complexes must be continuously synthesized, assembled and dismantled. The ubiquitin ligase UBR5 targets multiple transcription factors, such as the MYC oncoprotein, for degradation as unassembled orphan subunits. Transcription factors are constantly replenished de novo by protein synthesis, creating a dynamic system allowing cells to rapidly reorganize transcriptional ouput and modulate gene expression in response to the cellular environment. Importantly, these results suggest that orphan quality control ubiquitin ligases may be promising pharmacological targets for disrupting oncogenic gene expression programs.
