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Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression.

ABSTRACT: Yeast cells modulate their protein synthesis capacity in response to physiological needs through the transcriptional control of ribosomal protein (RP) genes. Here we demonstrate that the transcription factor Sfp1, previously shown to play a role in the control of cell size, regulates RP gene expression in response to nutrients and stress. Under optimal growth conditions, Sfp1 is localized to the nucleus, bound to the promoters of RP genes, and helps promote RP gene expression. In response to inhibition of target of rapamycin (TOR) signaling, stress, or changes in nutrient availability, Sfp1 is released from RP gene promoters and leaves the nucleus, and RP gene transcription is down-regulated. Additionally, cells lacking Sfp1 fail to appropriately modulate RP gene expression in response to environmental cues. We conclude that Sfp1 integrates information from nutrient- and stress-responsive signaling pathways to help control RP gene expression.

SUBMITTER: Marion RM

PROVIDER: S-EPMC521938 | biostudies-literature | 2004 Oct

REPOSITORIES: biostudies-literature

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Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression.

Marion Rosa M RM Regev Aviv A Segal Eran E Barash Yoseph Y Koller Daphne D Friedman Nir N O'Shea Erin K EK

Proceedings of the National Academy of Sciences of the United States of America 20040907 40

Yeast cells modulate their protein synthesis capacity in response to physiological needs through the transcriptional control of ribosomal protein (RP) genes. Here we demonstrate that the transcription factor Sfp1, previously shown to play a role in the control of cell size, regulates RP gene expression in response to nutrients and stress. Under optimal growth conditions, Sfp1 is localized to the nucleus, bound to the promoters of RP genes, and helps promote RP gene expression. In response to inh ...[more]

PMID: 15353587

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Project description:BackgroundThe high heterogeneity and the complexity of the tumor microenvironment of colorectal cancer (CRC) have enhanced the difficulty of prognosis prediction based on conventional clinical indicators. Recent studies revealed that tumor cells could overcome various nutritional deficiencies by gene regulation and metabolic remodeling. However, whether differentially expressed genes (DEGs) in CRC cells under kinds of nutrient deficiency could be used to predict prognosis remained unveiled.MethodsThree datasets (GSE70976, GSE13548, and GSE116087), in which colon cancer cells were, respectively, cultured in serum-free, glucose-free, or glutamine-free medium, were included to delineate the profiles of gene expression by nutrient stress. DEGs were figured out in three datasets, and gene functional analysis was performed. Survival analyses and Cox proportional hazards model were then used to identify nutrient stress sensitive genes in CRC datasets (GSE39582 and TCGA COAD). Then, a 5-gene signature was constructed and the risk scores were also calculated. Survival analyses, cox analyses, and nomogram were applied to predict the prognosis of patients with colorectal cancer. The effectiveness of the risk model was also tested.ResultsA total of 48 genes were found to be dysregulated in serum, glucose, or glutamine-deprived CRC cells, which were mainly enriched in cell cycle and endoplasmic reticulum stress pathways. After further analyses, 5 genes, MCM5, MCM6, CDCA2, GINS2, and SPC25, were identified to be differentially expressed in CRC and be related to prognosis of in CRC datasets. We used the above nutrient stress-sensitive genes to construct a risk scoring model. CRC samples in the datasets were divided into low-risk and high-risk groups. Data showed that higher risk scores were associated with better outcomes and risk scores decreased significantly with tumor procession. Moreover, the risk score could be used to predict the probability of survival based on nomogram.ConclusionsThe 5-nutrient stress-sensitive gene signature could act as an independent biomarker for survival prediction of CRC patients.

Dataset Information

Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression.

Publications

Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression.

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