The 14-3-3 proteins positively regulate rapamycin-sensitive signaling

Bertram, Paula; Zeng, Chenbo; Thorson, John; Shaw, Andréy S.; Zheng, X.F. Steven

doi:10.1016/s0960-9822(07)00535-0

Cited by 95 publications

(97 citation statements)

References 35 publications

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“…Deletion of only one BMH gene demonstrates no phenotypic differences under normal growth conditions. However, strains deleted in either BMH1 or BMH2 show increased sensitivity to rapamycin compared to parent strains (Bertram et al, 1998). Strains deleted in both 14-3-3 genes are normally inviable (Andoh et al, 1998;Gelperin et al, 1995;van Heusden et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

“…Although RAD24 and RAD25 appear to be functionally redundant, Rad25p has only marginal effects on resistance to UV resistance (Ford et al, 1994). In S. cerevisiae, the 14-3-3 proteins (Bmh1p and Bmh2p) are proposed to play a role in several signalling cascades, including the cAMP-dependent RAS-MAPK and TOR signalling pathways and vesicular transport (Beck and Hall, 1999;Bertram et al, 1998;Gelperin et al, 1995;Roberts et al, 1997;Roth et al, 1999). In the RAS-MAPK pathway, 14-3-3 proteins are essential for subsequent cell elongation, possibly by interacting with Ste20p (Roberts et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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The Candida albicans 14‐3‐3 gene, BMH1, is essential for growth

Cognetti

Davis

Sturtevant

2001

Yeast

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The 14-3-3 proteins are a family of conserved small acidic proteins that have been implicated in playing major roles in a wide variety of signalling cascades. In Saccharomyces cerevisiae, the 14-3-3 genes (BMH1 and BMH2) are essential for normal pseudohyphal induction and normal bud cell development. The Bmh proteins function in the cAMPdependent RAS/MAPK and rapamycin-sensitive signalling cascades. Deletion of only one BMH gene demonstrates no phenotypic differences under normal growth conditions. Strains deleted of both BMH1 and BMH2 are either non-viable or demonstrate sensitivity to environmental stresses. In Schizosaccharomyces pombe, the BMH homologues (RAD24 and RAD25) are essential for cell cycle control after DNA damage and deletion of both genes renders the cell inviable. The 14-3-3 gene in Candida albicans (BMH1) was identified using a novel adherence assay and differential display RT-PCR. Unlike other yeasts, C. albicans has only one 14-3-3 gene (BMH1). It was not possible to construct double knockouts by routine methods. These results suggested that the C. albicans BMH1 gene is essential. The essentiality of C. albicans BMH1 was confirmed by a PCR disruption technique. The C. albicans bmh1D/BMH1 heterozygotes exhibit growth and morphogenetic defects. Therefore, the BMH1 gene in C. albicans (Accession No. AF038154) is an excellent candidate to improve our understanding of the coordinate regulation of cell cycle and morphogenesis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Candida albicans 14‐3‐3 gene, BMH1, is essential for growth

Cognetti

Davis

Sturtevant

2001

Yeast

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“…5 The TOR (target of rapamycin) proteins, Tor1p and Tor2p, are phosphatidylinositol kinase-related kinases. TOR-mediated phosphorylation prevents nuclear accumulation of a number of nutrient-regulated transcription factors.…”

Section: Rapamycin-sentitive Signallingmentioning

confidence: 99%

“…38 ) BMH1 and BMH2 are multicopy suppressors of the growth inhibitory phenotype caused by rapamycin. 5 Conversely, deletion of BMH1 and BMH2 causes hypersensitivity to rapamycin, although there is no direct physical interaction between 14-3-3 and the TOR proteins. 5 The 14-3-3s act further downstream in the TOR pathway.…”

Section: Rapamycin-sentitive Signallingmentioning

confidence: 99%

“…5 Conversely, deletion of BMH1 and BMH2 causes hypersensitivity to rapamycin, although there is no direct physical interaction between 14-3-3 and the TOR proteins. 5 The 14-3-3s act further downstream in the TOR pathway. Bmh2p binds to the transcription factors Msn2p and Msn4p and retains the phosphorylated forms in the cytoplasm.…”

Section: Rapamycin-sentitive Signallingmentioning

confidence: 99%

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Yeast 14‐3‐3 proteins

Hemert

Heusden

Steensma

2001

Yeast

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14‐3‐3 Proteins

Cockrell

Acker

et al. 2009

Wiley Encyclopedia of Chemical Biology

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The 14‐3‐3 proteins are a family of multifunctional regulators in eukaryotic organisms. Through binding to over 200 client proteins, 14‐3‐3 proteins regulate numerous cellular functions, which include metabolic pathways, molecular trafficking, and cell‐cycle progression. Most 14‐3‐3 interactions are mediated by defined phosphoserine/threonine motifs within the target protein sequence. The presence of these phosphorylated motifs allows for integration of 14‐3‐3 interactions with client proteins into a diverse cellular signaling network, through the actions of various protein kinases and phosphatases. As evidence of its vital role in cell function, 14‐3‐3 has been implicated in human diseases, such as cancer and neuronal disorders. Thus, development of small‐molecule 14‐3‐3 modulators will allow the continued discovery of the critical importance of 14‐3‐3 in normal physiology and lead to future use as targeted therapies in human disease.

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The 14-3-3 proteins positively regulate rapamycin-sensitive signaling

Abstract: Our studies reveal 14-3-3 as an important component in rapamycin-sensitive signaling and provide significant new insights into the structure and function of 14-3-3 proteins.

Cited by 95 publications

References 35 publications

The Candida albicans 14‐3‐3 gene, BMH1, is essential for growth

The Candida albicans 14‐3‐3 gene, BMH1, is essential for growth

Yeast 14‐3‐3 proteins

14‐3‐3 Proteins

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