Regulation of G1/S transition in mammalian cells

Guevara, Claudia; Korver, Wouter; Mahony, Daniel; Seghezzi, Wolfgang; Shanahan, Fergus; Lees, Emma

doi:10.1046/j.1523-1755.1999.00711.x

Cited by 2 publications

(2 citation statements)

References 7 publications

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“…Unlike somatic cells, in which the G1 phase is marked by oscillating cyclin expression (Aleem et al, 2005;Guevara et al, 1999), G1 phase in the abbreviated cell cycle structure of both GSCs and mESCs is seemingly absent, with stem cells displaying a phaseindependent expression of the G1/S regulators CDK2 and cyclin E (Fox et al, 2011;White and Dalton, 2005). However, a mechanism for sustaining an abbreviated cell cycle structure with an abbreviated G1 remains unresolved.…”

Section: Introductionmentioning

confidence: 99%

GSK-3 promotes S-phase entry and progression in C. elegans germline stem cells to maintain tissue output

et al. 2018

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Adult germline stem cells (GSCs) and mouse embryonic stem cells (mESCs) exhibit a non-canonical cell cycle structure with an abbreviated G1 phase and phase-independent expression of Cdk2 and cyclin E. Mechanisms that promote the abbreviated cell cycle remain unknown, as do the consequences of not maintaining an abbreviated cell cycle in these tissues. In GSCs, we discovered that loss of results in reduced GSC proliferation without changes in differentiation or responsiveness to GLP-1/Notch signaling. We find that DPL-1 transcriptional activity inhibits CDK-2 mRNA accumulation in GSCs, which leads to slower S-phase entry and progression. Inhibition of or transgenic expression of CDK-2 via a heterologous germline promoter rescues the S-phase entry and progression defects of the mutants, demonstrating that transcriptional regulation rather than post-translational control of CDK-2 establishes the abbreviated cell cycle structure in GSCs. This highlights an inhibitory cascade wherein GSK-3 inhibits DPL-1 and DPL-1 inhibits transcription. Constitutive GSK-3 activity through this cascade maintains an abbreviated cell cycle structure to permit the efficient proliferation of GSCs necessary for continuous tissue output.

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Section: Introductionmentioning

confidence: 99%

GSK-3 promotes S-phase entry and progression in C. elegans germline stem cells to maintain tissue output

et al. 2018

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“…Unlike somatic cells’ G1 phase that is triggered and marked by increased amounts of cyclins E and D ( Aleem et al, 2005 ; Guevara et al, 1999 ), germ cells and ESCs are characterized by a shortened G1 phase and maintain a constitutive robust expression of G1/S regulators Cyclin E and CDK2 throughout the cell cycle ( Fox et al, 2011 ; Furuta et al, 2018 ; White and Dalton, 2005 ). Despite continuous proliferation of C. elegans SPCs, the SPC mitotic rate changes during development and in different mutant backgrounds ( Kocsisova et al, 2019 ; Michaelson et al, 2010 ; Roy et al, 2016 ), and it is unknown how SPC division and meiotic entry rates might be altered while maintaining the cell cycle with an abbreviated G1 phase.…”

Section: Introductionmentioning

confidence: 99%

Antagonistic control of Caenorhabditis elegans germline stem cell proliferation and differentiation by PUF proteins FBF-1 and FBF-2

Wang

Ellenbecker

Hickey

et al. 2020

eLife

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Stem cells support tissue maintenance, but the mechanisms that coordinate the rate of stem cell self-renewal with differentiation at a population level remain uncharacterized. We find that two PUF family RNA-binding proteins FBF-1 and FBF-2 have opposite effects on C. elegans germline stem cell dynamics: FBF-1 restricts the rate of meiotic entry, while FBF-2 promotes both cell division and meiotic entry rates. Antagonistic effects of FBFs are mediated by their distinct activities towards the shared set of target mRNAs, where FBF-1-mediated post-transcriptional control requires the activity of CCR4-NOT deadenylase, while FBF-2 is deadenylase-independent and might protect the targets from deadenylation. These regulatory differences depend on protein sequences outside of the conserved PUF family RNA-binding domain. We propose that the opposing FBF-1 and FBF-2 activities serve to modulate stem cell division rate simultaneously with the rate of meiotic entry.

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Regulation of G1/S transition in mammalian cells

Cited by 2 publications

References 7 publications

GSK-3 promotes S-phase entry and progression in C. elegans germline stem cells to maintain tissue output

GSK-3 promotes S-phase entry and progression in C. elegans germline stem cells to maintain tissue output

Antagonistic control of Caenorhabditis elegans germline stem cell proliferation and differentiation by PUF proteins FBF-1 and FBF-2

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