Concise Review: Fate Determination of Stem Cells by Deubiquitinating Enzymes

Chandrasekaran, Arun Pandian; Suresh, Bharathi; Kim, Hyongbum; Kim, Kye Seong; Ramakrishna, Suresh

doi:10.1002/stem.2446

Cited by 23 publications

(20 citation statements)

References 68 publications

(81 reference statements)

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“…It is likely that either the remaining MINDY protein was sufficient to support selfrenewal, or there is redundancy with another deubiquitinase present in ESCs. Many of the core self-renewal transcription factors are targets of the protein degradation machinery and their levels are regulated by a combination of transcriptional control and protein degradation [3,4]. We speculate that MINDY1 functions to prevent premature degradation of such proteins, thus promoting ESC self-renewal.…”

Section: Stem Cellsmentioning

confidence: 95%

“…In addition to transcriptional control, posttranslational modifications have been implicated in the regulation of stem cells. Regulation of proteasomal protein degradation by ubiquitination is essential for the maintenance of self-renewal and promotion of differentiation [3,4]. Despite the significant quantity of research on ESCs, there remains a lot to understand about the controls governing their decision to self-renew or differentiate.…”

Section: Introductionmentioning

confidence: 99%

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MINDY1 Is a Downstream Target of the Polyamines and Promotes Embryonic Stem Cell Self-Renewal

et al. 2018

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Embryonic stem cells have the ability to self-renew or differentiate and these processes are under tight control. We previously reported that the polyamine regulator AMD1 is critical for embryonic stem cell self-renewal. The polyamines putrescine, spermidine, and spermine are essential organic cations that play a role in a wide array of cellular processes. Here, we explore the essential role of the polyamines in the promotion of self-renewal and identify a new stem cell regulator that acts downstream of the polyamines: MINDY1. MINDY1 protein levels are high in embryonic stem cells (ESCs) and are dependent on high polyamine levels. Overexpression of MINDY1 can promote ESC self-renewal in the absence of the usually essential cytokine Leukemia Inhibitory Factor (LIF). MINDY1 protein is prenylated and this modification is required for its ability to promote self-renewal. We go on to show that Mindy1 RNA is targeted for repression by mir-710 during Neural Precursor cell differentiation. Taken together, these data demonstrate that high polyamine levels are required for ESC self-renewal and that they function, in part, through promotion of high MINDY1 levels. STEM CELLS 2018; 00:000-000 SIGNIFICANCE STATEMENTThis article shows that the polyamines, putrescine, spermidine, and spermine are essential for the maintenance of embryonic stem cell self-renewal. Inhibition of polyamine synthesis causes differentiation. This study identifies the MINDY1 protein as being a critical downstream target of the polyamines in driving self-renewal. MINDY1 functions to remove ubiquitin from target proteins this preventing their degradation. This study proposes that MINDY1 is a new critical regulator of stem cell self-renewal that functions to promote the stability of core self-renewal proteins.

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Section: Stem Cellsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

MINDY1 Is a Downstream Target of the Polyamines and Promotes Embryonic Stem Cell Self-Renewal

et al. 2018

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“…Ubiquitination and deubiquitination processes play a central role in the regulation of pluripotency and cell differentiation as reviewed elsewhere . In this review, we illustrate that in addition to the regulation of main pluripotency transcription factors, ubiquitin dynamics is responsible for other peculiar features of stem cells.…”

Section: Introductionmentioning

confidence: 83%

Ubiquitin Dynamics in Stem Cell Biology: Current Challenges and Perspectives

Dieuleveult

Miotto

2020

BioEssays

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Ubiquitination plays a central role in the regulation of stem cell self‐renewal, propagation, and differentiation. In this review, the functions of ubiquitin dynamics in a myriad of cellular processes, acting along side the pluripotency network, to regulate embryonic stem cell identity are highlighted. The implication of deubiquitinases (DUBs) and E3 Ubiquitin (Ub) ligases in cellular functions beyond protein degradation is reported, including key functions in the regulation of mRNA stability, protein translation, and intra‐cellular trafficking; and how it affects cell metabolism, the micro‐environment, and chromatin organization is discussed. Finally, unsolved issues in the field are emphasized and will need to be tackled in order to fully understand the contribution of ubiquitin dynamics to stem cell self‐renewal and differentiation.

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“…Post-translational modification by ubiquitin is a key regulator process for stem cell fate determination. Ubiquitination and deubiquitination are the major cellular processes used to balance the protein turnover of several transcription factors that regulate stem cell differentiation [144,145]. Cross-regulation between E3 ligases and DUBs for stem cell transcription factors is important in the regulation of stem cell function, including pluripotency, differentiation, and self-renewal.…”

Section: Otus and Stem Cellsmentioning

confidence: 99%

The function and regulation of OTU deubiquitinases

Sui

et al. 2019

Front. Med.

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Post-translational modification of cellular proteins by ubiquitin regulates numerous cellular processes, including cell division, immune responses, and apoptosis. Ubiquitin-mediated control over these processes can be reversed by deubiquitinases (DUBs), which remove ubiquitin from target proteins and depolymerize polyubiquitin chains. Recently, much progress has been made in the DUBs. In humans, the ovarian tumor protease (OTU) subfamily of DUBs includes 16 members, most of which mediate cell signaling cascades. These OTUs show great variation in structure and function, which display a series of mechanistic features. In this review, we provide a comprehensive analysis of current progress in character, structure and function of OTUs, such as the substrate specificity and catalytic activity regulation. Then we discuss the relationship between some diseases and OTUs. Finally, we summarize the structure of viral OTUs and their function in immune escape and viral survival. Despite the challenges, OTUs might provide new therapeutic targets, due to their involvement in key regulatory processes.

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Concise Review: Fate Determination of Stem Cells by Deubiquitinating Enzymes

Cited by 23 publications

References 68 publications

MINDY1 Is a Downstream Target of the Polyamines and Promotes Embryonic Stem Cell Self-Renewal

MINDY1 Is a Downstream Target of the Polyamines and Promotes Embryonic Stem Cell Self-Renewal

Ubiquitin Dynamics in Stem Cell Biology: Current Challenges and Perspectives

The function and regulation of OTU deubiquitinases

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