Dataset Information

An atypical unfolded protein response in heat shocked cells.

ABSTRACT:

Background

The heat shock response (HSR) and the unfolded protein response (UPR) are both activated by proteotoxic stress, although in different compartments, and share cellular resources. How these resources are allocated when both responses are active is not known. Insight in possible crosstalk will help understanding the consequences of failure of these systems in (age-related) disease.

Results

In heat stressed HEK293 cells synthesis of the canonical UPR transcription factors XBP1s and ATF4 was detected as well as HSF1 independent activation of the promoters of the ER resident chaperones HSPA5 (BiP) and DNAJB9 (ERdj4). However, the heat stress activation of the DNAJB9 promoter, a XBP1s target, was not blocked in cells expressing a dominant negative IRE1? mutant, and thus did not require XBP1s. Furthermore, the DNA element required for heat stress activation of the DNAJB9 promoter is distinct from the ATF4 and ATF6 target elements; even though inhibition of eIF2? phosphorylation resulted in a decreased activation of the DNAJB9 promoter upon heat stress, suggesting a role for an eIF2? phosphorylation dependent product.

Conclusions

The initial step in the UPR, synthesis of transcription factors, is activated by heat stress but the second step, transcriptional transactivation by these factors, is blocked and these pathways of the UPR are thus not productive. Expression of canonical ER chaperones is part of the response of heat stressed cells but another set of transcription factors has been recruited to regulate expression of these ER chaperones.

SUBMITTER: Heldens L

PROVIDER: S-EPMC3154502 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Publications

An atypical unfolded protein response in heat shocked cells.

Heldens Lonneke L Hensen Sanne M M SM Onnekink Carla C van Genesen Siebe T ST Dirks Ron P RP Lubsen Nicolette H NH

PloS one 20110810 8

<h4>Background</h4>The heat shock response (HSR) and the unfolded protein response (UPR) are both activated by proteotoxic stress, although in different compartments, and share cellular resources. How these resources are allocated when both responses are active is not known. Insight in possible crosstalk will help understanding the consequences of failure of these systems in (age-related) disease.<h4>Results</h4>In heat stressed HEK293 cells synthesis of the canonical UPR transcription factors X ...[more]

PMID: 21853144

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Project description:Adverse environmental conditions such as heat and salt stress create endoplasmic reticulum (ER) stress in maize and set off the unfolded protein response (UPR). A key feature of the UPR is the upregulation of ZmbZIP60 and the splicing of its messenger RNA. We conducted an association analysis of a recombinant inbred line (RIL) derived from a cross of a tropical founder line, CML52 with a standard temperate line, B73. We found a major QTL conditioning heat-induced ZmbZIP60 expression located cis to the gene. Based on the premise that the QTL might be associated with the ZmbZIP60 promoter, we evaluated various maize inbred lines for their ability to upregulate the expression of ZmbZIP60 in response to heat stress. In general, tropical lines with promoter regions similar to CML52 were more robust in upregulating ZmbZIP60 in response to heat stress. This finding was confirmed by comparing the strength of the B73 and CML52 ZmbZIP60 promoters in transient maize protoplast assays. We concluded that the upstream region of ZmbZIP60 is important in conditioning the response to heat stress and was under selection in maize when adapted to different environments. Summary: Heat stress has large negative effects on maize grain yield. Heat stress creates ER stress in maize and sets off the UPR. We searched for factors conditioning heat induction of the UPR in maize seedlings by conducting an association analysis based on the upregulation of unspliced and spliced forms of ZmbZIP60 mRNA (ZmbZIP60u and ZmbZIP60s, respectively). ZmbZIP60u was upregulated more robustly by heat stress in the tropical maize line, CML52, than in B73, and a major QTL derived from the analysis of RILs from a cross of these two lines mapped in the vicinity of ZmbZIP60. We conducted a cis/trans test to determine whether the QTL was acting as a cis regulatory element or in trans, as might be expected for a transcription factor. We found that the QTL was acting in cis, likely involving the ZmbZIP60 promoter. ZmbZIP60 promoters in other temperate and tropical lines similar to CML52 showed enhanced expression of ZmbZIP60u by heat. The contribution of the CML52 promoter to heat induction of ZmbZIP60 was confirmed by analyzing the CML52 and B73 promoters linked to a luciferase reporter and assayed in heat-treated maize protoplasts.

Dataset Information

An atypical unfolded protein response in heat shocked cells.

Background

Results

Conclusions

Publications

An atypical unfolded protein response in heat shocked cells.

Similar Datasets

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