The Role of E3s in Regulating Pluripotency of Embryonic Stem Cells and Induced Pluripotent Stem Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Jan 28

PMID 33503896

Citations 2

Authors

Yahong Wu

Weiwei Zhang

Affiliations

Soon will be listed here.

Abstract

Pluripotent embryonic stem cells (ESCs) are derived from early embryos and can differentiate into any type of cells in living organisms. Induced pluripotent stem cells (iPSCs) resemble ESCs, both of which serve as excellent sources to study early embryonic development and realize cell replacement therapies for age-related degenerative diseases and other cell dysfunction-related illnesses. To achieve these valuable applications, comprehensively understanding of the mechanisms underlying pluripotency maintenance and acquisition is critical. Ubiquitination modifies proteins with Ubiquitin (Ub) at the post-translational level to monitor protein stability and activity. It is extensively involved in pluripotency-specific regulatory networks in ESCs and iPSCs. Ubiquitination is achieved by sequential actions of the Ub-activating enzyme E1, Ub-conjugating enzyme E2, and Ub ligase E3. Compared with E1s and E2s, E3s are most abundant, responsible for substrate selectivity and functional diversity. In this review, we focus on E3 ligases to discuss recent progresses in understanding how they regulate pluripotency and somatic cell reprogramming through ubiquitinating core ESC regulators.

Citing Articles

DNA-damage orchestrates self-renewal and differentiation via reciprocal p53 family and Hippo/Wnt/TGF-β pathway activation in embryonic stem cells.

Ye Y, Xie W, Wang X, Tan S, Yang L, Ma Z Cell Mol Life Sci. 2025; 82(1):38.

PMID: 39762370 PMC: 11704118. DOI: 10.1007/s00018-024-05561-0.

Bivalent Regulation and Related Mechanisms of H3K4/27/9me3 in Stem Cells.

Sun H, Wang Y, Wang Y, Ji F, Wang A, Yang M Stem Cell Rev Rep. 2021; 18(1):165-178.

PMID: 34417934 DOI: 10.1007/s12015-021-10234-7.

References

Fuchs G, Shema E, Vesterman R, Kotler E, Wolchinsky Z, Wilder S . RNF20 and USP44 regulate stem cell differentiation by modulating H2B monoubiquitylation. Mol Cell. 2012; 46(5):662-73. PMC: 3374598. DOI: 10.1016/j.molcel.2012.05.023. View

Nie Z, Hu G, Wei G, Cui K, Yamane A, Resch W . c-Myc is a universal amplifier of expressed genes in lymphocytes and embryonic stem cells. Cell. 2012; 151(1):68-79. PMC: 3471363. DOI: 10.1016/j.cell.2012.08.033. View

Buganim Y, Faddah D, Cheng A, Itskovich E, Markoulaki S, Ganz K . Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase. Cell. 2012; 150(6):1209-22. PMC: 3457656. DOI: 10.1016/j.cell.2012.08.023. View

Hann S, Eisenman R . Proteins encoded by the human c-myc oncogene: differential expression in neoplastic cells. Mol Cell Biol. 1984; 4(11):2486-97. PMC: 369080. DOI: 10.1128/mcb.4.11.2486-2497.1984. View

Gu H, Li Q, Huang S, Lu W, Cheng F, Gao P . Mitochondrial E3 ligase March5 maintains stemness of mouse ES cells via suppression of ERK signalling. Nat Commun. 2015; 6:7112. PMC: 4458872. DOI: 10.1038/ncomms8112. View

Brons I, Smithers L, Trotter M, Rugg-Gunn P, Sun B, Chuva de Sousa Lopes S . Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature. 2007; 448(7150):191-5. DOI: 10.1038/nature05950. View

Novak D, Huser L, Elton J, Umansky V, Altevogt P, Utikal J . SOX2 in development and cancer biology. Semin Cancer Biol. 2019; 67(Pt 1):74-82. DOI: 10.1016/j.semcancer.2019.08.007. View

Boname J, Thomas M, Stagg H, Xu P, Peng J, Lehner P . Efficient internalization of MHC I requires lysine-11 and lysine-63 mixed linkage polyubiquitin chains. Traffic. 2009; 11(2):210-20. PMC: 3551259. DOI: 10.1111/j.1600-0854.2009.01011.x. View

Wang J, Zhang Y, Hou J, Qian X, Zhang H, Zhang Z . Ube2s regulates Sox2 stability and mouse ES cell maintenance. Cell Death Differ. 2015; 23(3):393-404. PMC: 5072435. DOI: 10.1038/cdd.2015.106. View

10.

Martello G, Smith A . The nature of embryonic stem cells. Annu Rev Cell Dev Biol. 2014; 30:647-75. DOI: 10.1146/annurev-cellbio-100913-013116. View

11.

Xu H, Wang W, Li C, Yu H, Yang A, Wang B . WWP2 promotes degradation of transcription factor OCT4 in human embryonic stem cells. Cell Res. 2009; 19(5):561-73. DOI: 10.1038/cr.2009.31. View

12.

Napolitano L, Jaffray E, Hay R, Meroni G . Functional interactions between ubiquitin E2 enzymes and TRIM proteins. Biochem J. 2010; 434(2):309-19. DOI: 10.1042/BJ20101487. View

13.

Nakagawa T, Kajitani T, Togo S, Masuko N, Ohdan H, Hishikawa Y . Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation. Genes Dev. 2008; 22(1):37-49. PMC: 2151013. DOI: 10.1101/gad.1609708. View

14.

Endoh M, Endo T, Endoh T, Fujimura Y, Ohara O, Toyoda T . Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity. Development. 2008; 135(8):1513-24. DOI: 10.1242/dev.014340. View

15.

Papaioannou V, McBurney M, Gardner R, Evans M . Fate of teratocarcinoma cells injected into early mouse embryos. Nature. 1975; 258(5530):70-73. DOI: 10.1038/258070a0. View

16.

Martin G, Evans M . The morphology and growth of a pluripotent teratocarcinoma cell line and its derivatives in tissue culture. Cell. 1974; 2(3):163-72. DOI: 10.1016/0092-8674(74)90090-7. View

17.

Jiang J, Chan Y, Loh Y, Cai J, Tong G, Lim C . A core Klf circuitry regulates self-renewal of embryonic stem cells. Nat Cell Biol. 2008; 10(3):353-60. DOI: 10.1038/ncb1698. View

18.

Mattout A, Meshorer E . Chromatin plasticity and genome organization in pluripotent embryonic stem cells. Curr Opin Cell Biol. 2010; 22(3):334-41. DOI: 10.1016/j.ceb.2010.02.001. View

19.

Dunn S, Martello G, Yordanov B, Emmott S, Smith A . Defining an essential transcription factor program for naïve pluripotency. Science. 2014; 344(6188):1156-1160. PMC: 4257066. DOI: 10.1126/science.1248882. View

20.

Liu C, Zhang D, Shen Y, Tao X, Liu L, Zhong Y . DPF2 regulates OCT4 protein level and nuclear distribution. Biochim Biophys Acta. 2015; 1853(12):3279-93. DOI: 10.1016/j.bbamcr.2015.09.029. View