Regulation of pluripotency and differentiation by deubiquitinating enzymes.
Post-translational modifications (PTMs) of stemness-related proteins are essential for stem cell maintenance and differentiation. In stem cell self-renewal and differentiation, PTM of stemness-related proteins is tightly regulated because the modified proteins execute various stem cell fate choices. Ubiquitination and deubiquitination, which regulate protein turnover of several stemness-related proteins, must be carefully coordinated to ensure optimal embryonic stem cell maintenance and differentiation. Deubiquitinating enzymes (DUBs), which specifically disassemble ubiquitin chains, are a central component in the ubiquitin-proteasome pathway. These enzymes often control the balance between ubiquitination and deubiquitination. To maintain stemness and achieve efficient differentiation, the ubiquitination and deubiquitination molecular switches must operate in a balanced manner. Here we summarize the current information on DUBs, with a focus on their regulation of stem cell fate determination and deubiquitinase inhibition as a therapeutic strategy. Furthermore, we discuss the possibility of using DUBs with defined stem cell transcription factors to enhance cellular reprogramming efficiency and cell fate conversion. Our review provides new insight into DUB activity by emphasizing their cellular role in regulating stem cell fate. This role paves the way for future research focused on specific DUBs or deubiquitinated substrates as key regulators of pluripotency and stem cell differentiation.
Department of Pharmacology and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
B
B
Suresh
Department of Physiology and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
J
J
Lee
Department of Pharmacology and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
H
H
Kim
Graduate School of Biomedical Science and Engineering, Department of Biomedical Science, Hanyang University, Seoul, South Korea.|College of Medicine, Department of Biomedical Science, Hanyang University, Seoul, South Korea.
S
S
Ramakrishna
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D000066673:Cell Self Renewal / Q000502:physiology*; D000072017:Deubiquitinating Enzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination
D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin; D000072017:Deubiquitinating Enzymes