The role of MAP4K3 in lifespan regulation of Caenorhabditis elegans

Khan, Maruf; Hart, Matthew J.; Rea, Shane L.

doi:10.1016/j.bbrc.2012.07.113

Cited by 6 publications

(8 citation statements)

References 27 publications

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“…; Khan et al. ) and the gene Psa , known to interact with the major IIS/TOR core component Akt1 (Vinayagam et al. ).…”

Section: Resultsmentioning

confidence: 99%

“…discussion in Remolina et al 2012;Fabian et al 2018;Flatt and Partridge 2018), we only found a few loci in this signaling network among our candidates. For instance, among the loci significantly differentiated between the E and P populations, we identified the TOR signaling gene happyhour (Bryk et al 2010;Khan et al 2012) and the gene Psa, known to interact with the major IIS/TOR core component Akt1 (Vinayagam et al 2016). Similarly, among the loci that differentiate the LE populations from the other EE populations we identified Tomosyn, a regulator of insulin secretion with a confirmed role in aging in C. elegans (Ch'ng et al 2008), as well as Pi3K21B and PKCδ, which both play a role in signal transduction from the insulin receptor (Braiman et al 2001;Teleman 2010).…”

Section: Different From 'Canonical' Longevity Genesmentioning

confidence: 99%

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Distinct genomic signals of lifespan and life history evolution in response to postponed reproduction and larval diet inDrosophila

et al. 2019

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Reproduction and diet are two major factors controlling the physiology of aging and life history, but how they interact to affect the evolution of longevity is unknown. Moreover, although studies of large‐effect mutants suggest an important role of nutrient sensing pathways in regulating aging, the genetic basis of evolutionary changes in lifespan remains poorly understood. To address these questions, we analyzed the genomes of experimentally evolved Drosophila melanogaster populations subjected to a factorial combination of two selection regimes: reproductive age (early versus postponed), and diet during the larval stage (“low,” “control,” “high”), resulting in six treatment combinations with four replicate populations each. Selection on reproductive age consistently affected lifespan, with flies from the postponed reproduction regime having evolved a longer lifespan. In contrast, larval diet affected lifespan only in early‐reproducing populations: flies adapted to the “low” diet lived longer than those adapted to control diet. Here, we find genomic evidence for strong independent evolutionary responses to either selection regime, as well as loci that diverged in response to both regimes, thus representing genomic interactions between the two. Overall, we find that the genomic basis of longevity is largely independent of dietary adaptation. Differentiated loci were not enriched for “canonical” longevity genes, suggesting that naturally occurring genic targets of selection for longevity differ qualitatively from variants found in mutant screens. Comparing our candidate loci to those from other “evolve and resequence” studies of longevity demonstrated significant overlap among independent experiments. This suggests that the evolution of longevity, despite its presumed complex and polygenic nature, might be to some extent convergent and predictable.

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“…; Khan et al. ) and the gene Psa , known to interact with the major IIS/TOR core component Akt1 (Vinayagam et al. ).…”

Section: Resultsmentioning

confidence: 99%

Section: Different From 'Canonical' Longevity Genesmentioning

confidence: 99%

Distinct genomic signals of lifespan and life history evolution in response to postponed reproduction and larval diet inDrosophila

et al. 2019

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“…gck-2(ok2867) is an in-frame 549-bp deletion in exon 5, resulting in deletion of a part of the kinase domain. gck-2(tm2537) is an out-of-frame 565-bp deletion in exon 5, resulting in early stop codons (Khan et al, 2012). Most genetics were done using these alleles and gck-2 -directed bacterially mediated RNAi (clone V-4P08; Figure 3A).…”

Section: Resultsmentioning

confidence: 99%

“…Deletions in gck-2 were detected by triplex primers REW88/89/90 (Tm: 58oC, 32 cycles), resulting in 298 bp (wild-type), 478 bp ( ok2867 ), and 462 bp ( tm2537 ) amplicons. PCR products were sequenced to confirm reported allele perturbations (Khan et al, 2012). The exoc-8(ok2523) deletion was detected by triplex primers REW109/110/111 (Tm: 58oC, 32 cycles), resulting in 411 bp (wild-type) and 270 bp ( ok2523 ) amplicons.…”

Section: Star+methodsmentioning

confidence: 99%

Ral Signals through a MAP4 Kinase-p38 MAP Kinase Cascade in C. elegans Cell Fate Patterning

et al. 2018

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C. elegans vulval precursor cell (VPC) fates are patterned by an epidermal growth factor (EGF) gradient. High-dose EGF induces 1° VPC fate, and lower dose EGF contributes to 2° fate in support of LIN-12/Notch. We previously showed that the EGF 2°-promoting signal is mediated by LET-60/Ras switching effectors, from the canonical Raf-MEK-ERK mitogen-activated protein (MAP) kinase cascade that promotes 1° fate to the non-canonical RalGEF-Ral that promotes 2° fate. Of oncogenic Ras effectors, RalGEF-Ral is by far the least well understood. We use genetic analysis to identify an effector cascade downstream of C. elegans RAL-1/Ral, starting with an established Ral binding partner, Exo84 of the exocyst complex. Additionally, RAL-1 signals through GCK-2, a citron-N-terminal-homology-domain-containing MAP4 kinase, and PMK-1/p38 MAP kinase cascade to promote 2° fate. Our study delineates a Ral-dependent developmental signaling cascade in vivo, thus providing the mechanism by which lower EGF dose is transduced.

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“…In addition, this study showed that miR-26a reduced the expression of MAP4K3 in both melanoma cell lines. MAP4K3 is a Ser/Thr kinase that is believed to regulate the activation of mTOR pathway, 42 which is crucial in regulating cell proliferation, cell growth, and inducing autophagy. 43 A variety of cancers can be caused by hyperactivation of the mTOR pathway.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-26a inhibits the growth and invasiveness of malignant melanoma and directly targets on MITF gene

2017

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Metastatic melanoma is the most aggressive form of skin cancer and is refractory to therapy. MicroRNAs have been recently discovered as novel molecules that provide therapeutic benefits against melanoma. This work aims to examine the effects of miR-26a and let-7a on the growth and invasiveness of malignant melanoma in vitro and in vivo. In addition, we elucidate the mechanism of action by identifying the target gene of miR-26a. Both miR-26a and let-7a inhibited proliferation and invasiveness and halted the cell cycle at the G 1 /G 0 phase in SKMEL-28 and WM1552C malignant melanoma cell lines. Moreover, miR-26a potently induced apoptosis and downregulated the expressions of microphthalmia-associated transcription factor (MITF) and MAP4K3 in both cell lines. The luciferase reporter assay demonstrated that miR-26a suppresses MITF expression by binding the 3′-UTR, suggesting that MITF is a bona fide target of miR-26a. SiRNA knockdown of the MITF gene confirmed that miR-26a reduced cell viability and induced apoptosis by regulating MITF. Using a murine model, we also found miR-26a significantly retarded the growth of melanoma tumors in vivo. In conclusion, miR-26a and let-7a suppressed the growth and invasiveness of melanoma cells, suggesting that miR-26a and let-7a may represent novel therapies for malignant melanoma.

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The role of MAP4K3 in lifespan regulation of Caenorhabditis elegans

Cited by 6 publications

References 27 publications

Distinct genomic signals of lifespan and life history evolution in response to postponed reproduction and larval diet inDrosophila

Distinct genomic signals of lifespan and life history evolution in response to postponed reproduction and larval diet inDrosophila

Ral Signals through a MAP4 Kinase-p38 MAP Kinase Cascade in C. elegans Cell Fate Patterning

MicroRNA-26a inhibits the growth and invasiveness of malignant melanoma and directly targets on MITF gene

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