Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One important promoter element at the 5' end of the c-fos gene is the serum response element (SRE). SRE is the site of attachment of the 67-kDa protein serum response factor (SRF) and several accessory proteins (Elk1, SAP1, SAP2/NET), termed the ternary complex factors. The binding of SRF to SRE plays an integral role in c-fos transcription and may occur independently of the association of the ternary complex factors. In the current study, we found that SRF protein expression was increased in the hearts of the old vs young adult rats in the basal condition. The hearts of old rats may have posttranslationally modified SRF proteins that are different compared to that of the young adults. The SRF increase was present both in the cytoplasm as well as in the nucleus in the old hearts. To test whether SRF protein levels in response to acute stress might be altered with age, we studied hearts of young adult and old rats during myocardial infarction. The young adult rat hearts responded to acute ischemic stress with an increase in both p62 and p67 SRF. The hearts of the old rats, however, did not exhibit a significant change in SRF protein expression. These findings demonstrate qualitative as well as quantitative age differences in SRF protein levels, both at baseline and following stimulation. The reduced SRF expression in response to acute cardiac ischemic stress in the old rats might contribute to the observed age-related decrease in the induction of immediate early genes such as c-fos in the heart.
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PMID:SRF binding to SRE in the rat heart: influence of age. 946 16

There is a reciprocal change in the expression of two members of the BAG (Bcl-2-associated athanogen) family, BAG1 and BAG3, during cellular aging and under acute stress ("BAG1-BAG3-switch"). BAG3 was recently described as a mediator of a novel macroautophagy pathway that uses the specificity of heat shock protein 70 (HSP70) to misfolded proteins and also involves other protein partners, such as HSPB8. Also crucial for induction and execution of autophagy are sequestosome-1/p62 (SQSTM1/p62) and LC3, an autophagosome-associated protein. In this novel pathway, BAG3 mediates the targeting and transport of degradation-prone substrates into aggresomes via the microtubule-motor dynein. Interestingly, aggresome-targeting by BAG3 does not depend on substrate ubiquitination and is, therefore, involved in the clearance of misfolded proteins that are not ubiquitinated.
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PMID:BAG3 and friends: co-chaperones in selective autophagy during aging and disease. 2168 Oct 22

The Nrf2 transcription factor belongs to the Cap'n'collar family, named after the founding member of this group, the product of the Drosophila Cap'n'collar gene. The encoded protein, Cap'n'collar, abbreviated Cnc, offers a convenient and accessible model to study the structure, function, and biology of Nrf2 transcription factors at the organismic, tissular, cellular, and molecular levels, using the powerful genetic, genomic, and biochemical tools available in Drosophila. In this review we provide an account of the original identification of Cnc as a regulator of embryonic development. We then describe the discovery of Nrf2-like functions of Cnc and its role in acute stress signaling and aging. The establishment of Drosophila as a model organism in which the mechanisms and functions of Nrf2 signaling can be studied has led to several discoveries: the regulation of stem cell activity by an Nrf2-mediated redox mechanism, the interaction of Nrf2 with p62 and Myc in the control of tissue growth and the unfolded protein response, and more. Several of these more recent lines of investigation are highlighted. Model organisms such as the fly and the worm remain powerful experimental platforms that can help to unravel the many remaining puzzles regarding the role of Nrf2 and its relatives in controlling the physiology and maintaining the health of multicellular organisms.
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PMID:Mechanisms and functions of Nrf2 signaling in Drosophila. 2611 22

In neurons, but also in all other cells the complex proteostasis network is monitored and tightly regulated by the cellular protein quality control (PQC) system. Beyond folding of newly synthesized polypeptides and their refolding upon misfolding the PQC also manages the disposal of aberrant proteins either by the ubiquitin-proteasome machinery or by the autophagic-lysosomal system. Aggregated proteins are primarily degraded by a process termed selective macroautophagy (or aggrephagy). One such recently discovered selective macroautophagy pathway is mediated by the multifunctional HSP70 co-chaperone BAG3 (BCL-2-associated athanogene 3). Under acute stress and during cellular aging, BAG3 in concert with the molecular chaperones HSP70 and HSPB8 as well as the ubiquitin receptor p62/SQSTM1 specifically targets aggregation-prone proteins to autophagic degradation. Thereby, BAG3-mediated selective macroautophagy represents a pivotal adaptive safeguarding and emergency system of the PQC which is activated under pathophysiological conditions to ensure cellular proteostasis. Interestingly, BAG3-mediated selective macroautophagy is also involved in the clearance of aggregated proteins associated with age-related neurodegenerative disorders, like Alzheimer's disease (tau-protein), Huntington's disease (mutated huntingtin/polyQ proteins), and amyotrophic lateral sclerosis (mutated SOD1). In addition, based on its initial description BAG3 is an anti-apoptotic protein that plays a decisive role in other widespread diseases, including cancer and myopathies. Therefore, in the search for novel therapeutic intervention avenues in neurodegeneration, myopathies and cancer BAG3 is a promising candidate.
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PMID:The Role of the Multifunctional BAG3 Protein in Cellular Protein Quality Control and in Disease. 2868 Mar 91