Insulin Regulation of Gene Expression through the Forkhead Transcription Factor Foxo1 (Fkhr) Requires Kinases Distinct from Akt†

Biochemistry ◽  
2001 ◽  
Vol 40 (39) ◽  
pp. 11768-11776 ◽  
Author(s):  
Jun Nakae ◽  
Tadahiro Kitamura ◽  
Wataru Ogawa ◽  
Masato Kasuga ◽  
Domenico Accili
2004 ◽  
Vol 3 (4) ◽  
pp. 944-954 ◽  
Author(s):  
Richard Bulmer ◽  
Aline Pic-Taylor ◽  
Simon K. Whitehall ◽  
Kate A. Martin ◽  
Jonathan B. A. Millar ◽  
...  

ABSTRACT In eukaryotes the regulation of gene expression plays a key role in controlling cell cycle progression. Here, we demonstrate that a forkhead transcription factor, Fkh2, regulates the periodic expression of cdc15 + and spo12 + in the M and G1 phases of the cell division cycle in the fission yeast Schizosaccharomyces pombe. We also show that Fkh2 is important for several cell cycle processes, including cell morphology and cell separation, nuclear structure and migration, and mitotic spindle function. We find that the expression of fkh2 + is itself regulated in a cell cycle-dependent manner in G1 coincident with the expression of cdc18 +, a Cdc10-regulated gene. However, fkh2 + expression is independent of Cdc10 function. Fkh2 was found to be phosphorylated during the cell division cycle, with a timing that suggests that this posttranslational modification is important for cdc15 + and spo12 + expression. Related forkhead proteins regulate G2 and M phase-specific gene expression in the evolutionarily distant Saccharomyces cerevisiae, suggesting that these proteins play conserved roles in regulating cell cycle processes in eukaryotes.


2006 ◽  
Vol 20 (10) ◽  
pp. 2304-2314 ◽  
Author(s):  
Wei Wu ◽  
Min Zou ◽  
Deanna R. Brickley ◽  
Travis Pew ◽  
Suzanne D. Conzen

Abstract Activation of the glucocorticoid receptor (GR) plays a critical role in the stress response of virtually all cell types. Despite recent advances in large-scale genomic and proteomic data acquisition, identification of physiologically relevant molecular events downstream of nuclear hormone receptor activation remains challenging. By analyzing gene expression changes 30 min after dexamethasone (Dex) treatment, we previously found that immediate induction of serum and glucocorticoid-regulated kinase-1 (SGK-1) expression is required for GR-mediated mammary epithelial cell survival signaling. We now report that activation of the GR mediates Forkhead transcription factor 3a (FOXO3a) phosphorylation and inactivation in mammary epithelial cells. GR-mediated induction of SGK-1 expression is required for FOXO3a inactivation; additional growth factor stimulation is not required. To further explore the gene expression changes that occur downstream of GR-mediated FOXO3a inactivation, we analyzed temporal gene expression data and selected GR-down-regulated genes containing core FOXO3a binding motifs in their proximal promoters. This approach revealed several previously unrecognized transcriptional target genes of FOXO3a, including IGF binding protein-3 (IGFBP-3). Endogenous IGFBP-3 expression was confirmed to be dependent on the GR-SGK-1-FOXO3a signaling pathway. Moreover, GR activation decreased FOXO3a-induced apoptosis in SK-BR-3 breast cancer cells. Collectively, our data suggest that GR-mediated FOXO3a inactivation is an important mechanism contributing to glucocorticoid-mediated mammary epithelial cell survival.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 372 ◽  
Author(s):  
Delasa Aghamirzaie ◽  
Karthik Raja Velmurugan ◽  
Shuchi Wu ◽  
Doaa Altarawy ◽  
Lenwood S. Heath ◽  
...  

Motivation: The increasing availability of chromatin immunoprecipitation sequencing (ChIP-Seq) data enables us to learn more about the action of transcription factors in the regulation of gene expression. Even though in vivo transcriptional regulation often involves the concerted action of more than one transcription factor, the format of each individual ChIP-Seq dataset usually represents the action of a single transcription factor. Therefore, a relational database in which available ChIP-Seq datasets are curated is essential. Results: We present Expresso (database and webserver) as a tool for the collection and integration of available Arabidopsis ChIP-Seq peak data, which in turn can be linked to a user’s gene expression data. Known target genes of transcription factors were identified by motif analysis of publicly available GEO ChIP-Seq data sets. Expresso currently provides three services: 1) Identification of target genes of a given transcription factor; 2) Identification of transcription factors that regulate a gene of interest; 3) Computation of correlation between the gene expression of transcription factors and their target genes. Availability: Expresso is freely available at http://bioinformatics.cs.vt.edu/expresso/


2020 ◽  
Author(s):  
Nadav Eisner ◽  
Tzofia Maymon ◽  
Ester Cancho Sanchez ◽  
Dana Bar-Zvi ◽  
Sagie Brodsky ◽  
...  

AbstractThe transcription factor ABA-INSENSITIVE(ABI)4 has diverse roles in regulating plant growth, including inhibiting germination and reserve mobilization in response to ABA and high salinity, inhibiting seedling growth in response to high sugars, inhibiting lateral root growth, and repressing light-induced gene expression. ABI4 activity is regulated at multiple levels, including gene expression, protein stability, and activation by phosphorylation. Although ABI4 can be phosphorylated at multiple residues by MAPKs, we found that S114 is the preferred site of MPK3. To examine the possible biological role of S114 phosphorylation, we transformed abi4-1 mutant plants with ABI4pro::ABI4 constructs encoding wild type (114S), phosphorylation-null (S114A) or phosphomimetic (S114E) forms of ABI4. Phosphorylation of S114 is necessary for the response to ABA, glucose, salt stress, and lateral root development, where the abi4 phenotype could be complemented by expressing ABI4(114S) or ABI4(S114E) but not ABI4(S114A). Comparison of root transcriptomes in ABA-treated roots of abi4-1 mutant plants transformed with constructs encoding the different phosphorylation-forms of S114 of ABI4 revealed that 85% of the ABI4-regulated genes whose expression pattern could be restored by expressing ABI4(114S) are down-regulated by ABI4. Over half of the ABI4-modulated genes were independent of the phosphorylation state of ABI4; these are enriched for stress responses. Phosphorylation of S114 was required for regulation of 35% of repressed genes, but only 17% of induced genes. The genes whose repression requires the phosphorylation of S114 are mainly involved in embryo and seedling development, growth and differentiation, and regulation of gene expression.HighlightsTranscription factor ABI4 is a substrate of MAP kinases.MPK3 preferentially phosphorylates Serine 114 of ABI4.Phosphorylated Serine 114 of ABI4 is required for the complementation of abi4 mutants.Phosphorylated ABI4 acts primarily as a repressor.


2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Damian Kołat ◽  
Żaneta Kałuzińska ◽  
Andrzej K. Bednarek ◽  
Elżbieta Płuciennik

Abstract The Activator Protein 2 (AP-2) transcription factor (TF) family is vital for the regulation of gene expression during early development as well as carcinogenesis process. The review focusses on the AP-2α and AP-2γ proteins and their dualistic regulation of gene expression in the process of carcinogenesis. Both AP-2α and AP-2γ influence a wide range of physiological or pathological processes by regulating different pathways and interacting with diverse molecules, i.e. other proteins, long non-coding RNAs (lncRNA) or miRNAs. This review summarizes the newest information about the biology of two, AP-2α and AP-2γ, TFs in the carcinogenesis process. We emphasize that these two proteins could have either oncogenic or suppressive characteristics depending on the type of cancer tissue or their interaction with specific molecules. They have also been found to contribute to resistance and sensitivity to chemotherapy in oncological patients. A better understanding of molecular network of AP-2 factors and other molecules may clarify the atypical molecular mechanisms occurring during carcinogenesis, and may assist in the recognition of new diagnostic biomarkers.


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