Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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The CrebA/Creb3-like transcription factors are major and direct regulators of secretory capacity

ABSTRACT: Abstract: Secretion occurs in all cells, with relatively low levels in most cells and extremely high levels in specialized secretory cells, such as those of the pancreas, salivary and mammary glands. Here, we report that the CrebA/Creb3-like family of bZip transcription factors functions to upregulate expression of both the general protein machinery required in all cells for secretion and of cell-type specific secreted proteins. Drosophila CrebA directly binds the enhancers of secretory pathway genes and is both necessary and sufficient to activate expression of every secretory pathway component gene examined thus far. Microarray profiling reveals that CrebA also upregulates expression of genes encoding cell type specific secreted components. Finally, we find that the human CrebA orthologues, Creb3L1 and Creb3L2, have the ability to upregulate the secretory pathway in non-secretory cell types. This SuperSeries is composed of the following subset Series: GSE23334: Active Creb3L1 can upregulate secretory pathway genes in HeLa cells GSE23346: CrebA is a major and direct regulator of secretory pathway gene expression Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Deborah Andrew

PROVIDER: E-GEOD-23349 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The CrebA/Creb3-like transcription factors are major and direct regulators of secretory capacity.

Fox Rebecca M RM Hanlon Caitlin D CD Andrew Deborah J DJ

The Journal of cell biology 20101101 3

Secretion occurs in all cells, with relatively low levels in most cells and extremely high levels in specialized secretory cells, such as those of the pancreas, salivary, and mammary glands. How secretory capacity is selectively up-regulated in specialized secretory cells is unknown. Here, we find that the CrebA/Creb3-like family of bZip transcription factors functions to up-regulate expression of both the general protein machinery required in all cells for secretion and of cell type-specific se ...[more]

PMID: 21041443

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Project description:Investigation of whole genome gene expression level changes in Ashbya gossypii VTT D-101398 secreting recombinant endoglucanase I (EGI) from Trichoderma ressei (Ribeiro et al. 2010 - PMID: 20422178), compared to the its corresponding empty vector control strain and to conditions where VTT D-101398 EGI secreting cultures were treated with dithiothreitol (DTT). Background: Ashbya gossypii is a filamentous Saccharomycete used for the industrial production of riboflavin that has been recently explored as a host system for recombinant protein production. To gain insight into the protein secretory pathway of this biotechnologically relevant fungus, we undertook genome-wide analyses to explore its secretome and its transcriptional responses to protein secretion stress. Results: A computational pipeline was used to predict the inventory of proteins putatively secreted by A. gossypii via the general secretory pathway. The proteins actually secreted by this fungus into the supernatants of submerged cultures in minimal and rich medium were mapped by two-dimensional gel electrophoresis, revealing that most of the A. gossypii secreted proteins have an isoelectric point between 4 and 6, and a molecular mass above 25 kDa. These analyses together indicated that 1-4% of A. gossypii proteins are likely to be secreted, of which less than 33% are putative hydrolases. Furthermore, transcriptomic analyses carried out in A. gossypii cells under recombinant protein secretion conditions and dithiothreitol-induced secretion stress unexpectedly revealed that a conventional unfolded protein response (UPR) was not activated in any of the conditions, as the expression levels of several well-known UPR target genes (e.g. IRE1, KAR2, HAC1 and PDI1 homologs) remained unaffected. However, several other genes involved in protein unfolding, endoplasmatic reticulum-associated degradation, proteolysis, vesicle trafficking, vacuolar protein sorting, secretion and mRNA degradation were up-regulated by dithiothreitol-induced secretion stress. Conversely, the transcription of several genes encoding secretory proteins, such as components of the glycosylation pathway, was severely repressed by dithiothreitol Conclusions: This study provides the first insights into the secretion stress response of A. gossypii, as well as a basic understanding of its protein secretion potential, which is more similar to that of yeast than to that of other filamentous fungi. Contrary to what has been widely described for yeast and fungi, a conventional UPR was not observed in A. gossypii, but alternative protein quality control mechanisms enabled it to cope with secretion stress. These data will help provide strategies for improving heterologous protein secretion in A. gossypii.

Dataset Information

The CrebA/Creb3-like transcription factors are major and direct regulators of secretory capacity

Publications

The CrebA/Creb3-like transcription factors are major and direct regulators of secretory capacity.

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