Ubiquitin-Dependent Regulation of Stem Cell Biology

Werner, Achim; Manford, Andrew G.; Rapé, Michael

doi:10.1016/j.tcb.2017.04.002

Cited by 42 publications

(44 citation statements)

References 122 publications

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“…A key feature of the eukaryotic cell cycle is that Cyclin protein levels are rapidly degraded to promote entry into the succeeding cell cycle phase. This is accomplished by the interconnected activity of ubiquitin ligase complexes (reviewed in Thurlings and De Bruin, 2016;Werner et al, 2017;Yamano, 2019). The Cullin 4-containing Cullin-RING E3 ubiquitin ligase (CRL4) targets the transcription factor E2f1, signaling exit from S-phase.…”

Section: An Intrinsic Timer Likely Regulates Fusome-orchestrated Mitomentioning

confidence: 99%

Coordinating Proliferation, Polarity, and Cell Fate in the Drosophila Female Germline

Hinnant

Merkle

Ables

2020

Front. Cell Dev. Biol.

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Gametes are highly specialized cell types produced by a complex differentiation process. Production of viable oocytes requires a series of precise and coordinated molecular events. Early in their development, germ cells are an interconnected group of mitotically dividing cells. Key regulatory events lead to the specification of mature oocytes and initiate a switch to the meiotic cell cycle program. Though the chromosomal events of meiosis have been extensively studied, it is unclear how other aspects of oocyte specification are temporally coordinated. The fruit fly, Drosophila melanogaster, has long been at the forefront as a model system for genetics and cell biology research. The adult Drosophila ovary continuously produces germ cells throughout the organism's lifetime, and many of the cellular processes that occur to establish oocyte fate are conserved with mammalian gamete development. Here, we review recent discoveries from Drosophila that advance our understanding of how early germ cells balance mitotic exit with meiotic initiation. We discuss cell cycle control and establishment of cell polarity as major themes in oocyte specification. We also highlight a germline-specific organelle, the fusome, as integral to the coordination of cell division, cell polarity, and cell fate in ovarian germ cells. Finally, we discuss how the molecular controls of the cell cycle might be integrated with cell polarity and cell fate to maintain oocyte production.

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Section: An Intrinsic Timer Likely Regulates Fusome-orchestrated Mitomentioning

confidence: 99%

Coordinating Proliferation, Polarity, and Cell Fate in the Drosophila Female Germline

Hinnant

Merkle

Ables

2020

Front. Cell Dev. Biol.

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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%

“…[7,9] Ubiquitination and deubiquitination processes play a central role in the regulation of pluripotency and cell differentiation as reviewed elsewhere. [10][11][12] 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. We further discuss how these recent findings help better understand the complexity and the versatility of stem cells, and the remaining challenges in the field.…”

Section: Introductionmentioning

confidence: 99%

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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“…Regulation of protein stability as a determining factor in the fate switch from stem cell to differentiation is likely a broadly used mechanism (Werner, Manford, & Rape, 2017). Although few cases are thoroughly understood, examples exist in flies and human cells in addition to nematodes.…”

Section: Discussionmentioning

confidence: 99%

LST-1 acts in trans with a conserved RNA-binding protein to maintain stem cells

Haupt

Enright

Ferdous

et al. 2019

Preprint

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21 22 23 IMPACT STATEMENT 24 A key stem cell regulator partners with a broadly conserved PUF RNA-binding protein to drive self-25 renewal and maintain a stem cell pool.26 27 2 ABSTRACT 28Stem cell self-renewal is essential to development and tissue repair. The C. elegans LST-1 protein is a 29 pivotal regulator of self-renewal and oncogenic when misexpessed. Here we define regions within the 30 LST-1 protein that provide molecular insights into both its function and regulation. LST-1 self-renewal 31 activity resides within a predicted disordered region that harbors two KXXL motifs. These KXXL motifs 32 mediate LST-1 binding to FBF, a broadly conserved Pumilio/PUF RNA-binding protein that represses 33 differentiation. Point mutations of the KXXL motifs abrogate LST-1 self-renewal activity. Therefore, FBF 34 binding is essential to LST-1 function. A second distinct region regulates LST-1 spatial expression and 35 primarily affects LST-1 protein turnover. Upon loss of this regulatory region, LST-1 protein distribution 36 expands and drives formation of a larger than normal GSC pool. Thus, LST-1 promotes self-renewal as a 37 key FBF partner, and its spatial regulation helps determine size of the GSC pool.

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Ubiquitin-Dependent Regulation of Stem Cell Biology

Cited by 42 publications

References 122 publications

Coordinating Proliferation, Polarity, and Cell Fate in the Drosophila Female Germline

Coordinating Proliferation, Polarity, and Cell Fate in the Drosophila Female Germline

Ubiquitin Dynamics in Stem Cell Biology: Current Challenges and Perspectives

LST-1 acts in trans with a conserved RNA-binding protein to maintain stem cells

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