Abbreviations: DUB, deubiquitylating enzyme; ESCs, embryonic stem cells; ICM, inner cell mass; PTM, post-translational modification; iPSCs, induced pluripotent stem cells; USP, ubiquitin-specific processing protease; UCH, ubiquitin carboxy-terminal hydrolase; OUT, otu-domain ubiquitin aldehyde binding protein; JAMM, jad1/pad/mpn-domain-containing metalloenzyme; MCPIP, monocyte chemotactic protein-induced protease; PSC, pluripotent stem cell; CNS, central nervous system; CPP, cell penetrating

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... tide; piPS-Cs, protein-induced pluripotentstem cells; WWP2, ww domain-containing protein 2; UPS, ubiquitin proteasome system; MEFs, mouse embryonic fibroblasts; FBXW8, f-box/wd repeat-containing protein 8 Abstract In stem cell pluripotency and differentiation, ubiquitylation and deubiquitylation modifications of stem cell core transcription proteinsis of high significance, as it influences stem cell fate determination. Two key enzymes i.e. an E3 ubiquitin ligase enzyme; known for tagging ubiquitin molecules to the target proteins for degradation, and the deubiquitylating enzyme (DUB), that counteracts the proteolysis, have to be well balanced for cellular homeostasis. Interestingly, the notion of DUBs enhancing the stability and half-life of stem cell core transcription factors has presented a new vision about significance of applying DUBs to control stem cell fate determination and cellular reprogramming. In this review, we propose the applications of DUBs along with stem cells core transcription factors i.e. Oct4, Sox2, Klf4, c-Myc, Nanog and Lin28 for an efficient generation of protein induced pluripotent stem cells. Citation: Haq S, Ramakrishna S. Future application of deubiquitylating enzymes for rapid and efficient cellular reprogramming.