Cancers, Vol. 12, Pages 1548: Protein Stability of Pyruvate Kinase Isozyme M2 Is Mediated by HAUSP

Cancers, Vol. 12, Pages 1548: Protein Stability of Pyruvate Kinase Isozyme M2 Is Mediated by HAUSP Cancers doi: 10.3390/cancers12061548 Authors: Hae-Seul Choi Chang-Zhu Pei Jun-Hyeok Park Soo-Yeon Kim Seung-Yeon Song Gyeong-Jin Shin Kwang-Hyun Baek The ubiquitin–proteasome system (UPS) is responsible for proteasomal degradation, regulating the half-life of the protein. Deubiquitinating enzymes (DUBs) are components of the UPS and inhibit degradation by removing ubiquitins from protein substrates. Herpesvirus-associated ubiquitin-specific protease (HAUSP) is one such deubiquitinating enzyme and has been closely associated with tumor development. In a previous study, we isolated putative HAUSP binding substrates by two-dimensional electrophoresis (2-DE) and identified them by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF/MS) analysis. The analysis showed that pyruvate kinase isoenzyme M2 (PKM2) was likely to be one of the substrates for HAUSP. Further study revealed that PKM2 binds to HAUSP, confirming the interaction between these proteins, and that PKM2 possesses the putative HAUSP binding motif, E or P/AXXS. Therefore, we generated mutant forms of PKM2 S57A, S97A, and S346A, and found that S57A had less binding affinity. In a previous study, we demonstrated that PKM2 is regulated by the UPS, and that HAUSP- as a DUB-acted on PKM2, thus siRNA for HAUSP increases PKM2 ubiquitination. Our present study ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research