C. elegans DAF-18/PTEN Mediates Nutrient-Dependent Arrest of Cell Cycle and Growth in the Germline

Fukuyama, Masamitsu; Rougvie, Ann E.; Rothman, Joel H.

doi:10.1016/j.cub.2006.02.073

Cited by 181 publications

(246 citation statements)

References 33 publications

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“…S1A) (13)(14)(15)(16). Although it is less clear how the other two genes affect survival of starved L1 larvae, AMPK becomes activated in response to starvation and phosphorylates diverse substrates to facilitate metabolic adjustment (17).…”

Section: Significancementioning

confidence: 99%

AMPK blocks starvation-inducible transgenerational defects in Caenorhabditis elegans

Demoinet

Roy

2017

Proc. Natl. Acad. Sci. U.S.A.

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Life history events, such as traumatic stress, illness, or starvation, can influence us through molecular changes that are recorded in a pattern of characteristic chromatin modifications. These modifications are often associated with adaptive adjustments in gene expression that can persist throughout the lifetime of the organism, or even span multiple generations. Although these adaptations may confer some selective advantage, if they are not appropriately regulated they can also be maladaptive in a context-dependent manner. We show here that during periods of acute starvation in Caenorhabditis elegans larvae, the master metabolic regulator AMP-activated protein kinase (AMPK) plays a critical role in blocking modifications to the chromatin landscape. This ensures that gene expression remains inactive in the germ-line precursors during adverse conditions. In its absence, critical chromatin modifications occur in the primordial germ cells (PGCs) of emergent starved L1 larvae that correlate with compromised reproductive fitness of the generation that experienced the stress, but also in the subsequent generations that never experienced the initial event. Our findings suggest that AMPK regulates the activity of the chromatin modifying COMPASS complex (complex proteins associated with Set1) to ensure that chromatin marks are not established until nutrient/energy contingencies are satisfied. Our study provides molecular insight that links metabolic adaptation to transgenerational epigenetic modification in response to acute periods of starvation.epigenetics | AMPK | histone methyltransferase | COMPASS | C. elegans

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Section: Significancementioning

confidence: 99%

AMPK blocks starvation-inducible transgenerational defects in Caenorhabditis elegans

Demoinet

Roy

2017

Proc. Natl. Acad. Sci. U.S.A.

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“…In C. elegans the PTEN homolog (DAF-18) regulates aging and dauer formation by opposing AGE-1 (PI3K) (Ogg and Ruvkun, 1998). Recently, DAF-18 has also been shown to regulate nutrient-dependent cell cycle arrest in C. elegans, (Fukuyama et al, 2006). The roles of PTEN in Drosophila are broader than those described in worms.…”

Section: Introductionmentioning

confidence: 99%

The role of PTEN signaling perturbations in cancer and in targeted therapy

2008

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The PTEN tumor suppressor was discovered by its homozygous deletion and other mutations in cancer. Since then, PTEN has been shown to be a non-redundant, evolutionarily conserved phosphatase whose function affects diverse cellular progresses such as cell cycle progression, cell proliferation, chemotaxis, apoptosis, aging, muscle contractility, DNA damage response, angiogenesis and cell polarity. In accordance with its ability to influence multiple crucial cellular processes, PTEN has a major role in the pathogenesis of numerous diseases such as diabetes, autism and almost every cancer examined. This review will discuss the diverse ways in which PTEN signaling is modified in cancer, and how these changes correlate with and might possibly affect the action of targeted chemotherapy.

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“…Historically, CHK-1 is activated after either replication stress or DNA DSBs. 12 We could eliminate replication stress as a candidate, because Z2/Z3 finish replication during early embryogenesis, 11 and thus we focused on the possibility that nutrients were triggering DNA DSBs within Z2/Z3 nuclei. One cytological hallmark of DNA DSBs is the appearance of RAD-51 foci.…”

Section: Dna Damage Arises In Z2/z3 In a Nutrient-dependent Mannermentioning

confidence: 99%

Trouble in transitioning: activation of zygotic transcription can lead to DNA breakage and genome instability

Butuči

Wong²,

Michael

2015

Worm

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C. elegans DAF-18/PTEN Mediates Nutrient-Dependent Arrest of Cell Cycle and Growth in the Germline

Cited by 181 publications

References 33 publications

AMPK blocks starvation-inducible transgenerational defects in Caenorhabditis elegans

AMPK blocks starvation-inducible transgenerational defects in Caenorhabditis elegans

The role of PTEN signaling perturbations in cancer and in targeted therapy

Trouble in transitioning: activation of zygotic transcription can lead to DNA breakage and genome instability

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