IndraLab

"Nowadays, for the modification regulation of OTUB2, only SUMOylation of the Lys233 site of OTUB2 is confirmed to interact with Yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ), thereby enhancing the activity of OTUB2 and mediating the transfer of ubiquitin ( xref )."

"In mouse breast cancer cells, OTUB2 is SUMOylated at the Lys233 site after translation, and modified OTUB2 relies on this modification to interact with SUMO-interacting motif (SIM) of YAP/TAZ to perform its deubiquitination function, ultimately affecting cancer metastasis ( xref )."

"Interestingly, OTUB2 is sumoylated on Lys 233, which promotes its association with Yap/Taz via a conserved but previously uncharacterized SUMO-interacting motif (SIM) in Yap/Taz ( xref )."

"Ovarian tumor (OTU) domain-containing ubiquitin aldehyde-binding protein 2 (OTUB2) is an active-site cysteine containing DUB. xref Recent research progress revealed that elevated OTUB2 expression correlates with tumorigenesis and metastasis. xref − xref OTUB2 can promote tumorigenic progression of non-small cell lung cancer cells through deubiquitination of U2AF2, stimulation of the Warburg effect, and activation of AKT/mTOR signaling. xref Moreover, OTUB2 has been identified as a cancer stemness and metastasis-promoting factor that deubiquitinates YAP/TAZ proteins in breast cancer cells, whereby poly-SUMOylation on OTUB2 lysine 233 mediates the interaction with YAP/TAZ. xref These studies demonstrate OTUB2 to be a relevant therapeutic target, and the development of OTUB2-specific inhibitors can potentially be beneficial for cancer therapies."

"Furthermore, the SUMOylation of OTUB2 at Lys-233 facilitates its interaction with YAP/TAZ and augments its deubiquitinating activity xref ."

"OTUB2, a deubiquitinating cysteine protease, has been shown to deubiquitinate and activate YAP/TAZ in RAS-transformed MCF10A cells, which is dependent on poly-SUMOylation of OTUB2 on lysine 233 ( xref ) [ xref ]."

"For instance, SUMOylation of the deubiquitinating enzyme OTUB2 at K233 heightens its interaction with YAP/TAZ and stabilizes YAP/TAZ via deubiquitination, contributing to cancer metastasis xref ."