The E3 ubiquitin ligase SPRYD3-MYCBP2(PAM) regulates mitotic cell fate and ubiquitination of USP11 to control spindle assembly

We show that the atypical E3 ligase MYCBP2 binds to the SPRY-domain containing protein SPRYD3 to form a new E3 ubiquitin ligase complex. We identified the DUB USP11 as the first substrate of MYCBP2/SPRYD3. Interestingly, USP11 is ubiquitinated by MYCBP2/SPRYD3 on a cysteine residue, C318, leading to proper bipolar spindle formation and mitotic slippage in cells treated with microtubule (MT) poisons.