Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 78-kDa glucose-regulated protein (GRP78) is ubiquitously expressed in many cell types. Its promoter contains multiple protein-binding sites and functional elements. In this study we examined a high affinity protein-binding site spanning bp -198 to -180 of the rat grp78 promoter, using nuclear extracts from both B-lymphoid and HeLa cells. This region contains a sequence TGACGTGA which, with the exception of one base, is identical to the cAMP-response element (CRE). Site-directed mutagenesis reveals that this sequence functions as a major basal level regulatory element in hamster fibroblast cells and is also necessary to maintain high promoter activity under stress-induced conditions. By gel mobility shift analysis, we detect two specific protein complexes. The major specific complex I, while immunologically distinct from the 42-kDa CRE-binding protein (CREB), binds most strongly to the grp site, but also exhibits affinity for the CRE consensus sequence. As such, complex I may consist of other members of the CREB/activating transcription factor protein family. The minor specific complex II consists of CREB or a protein antigenically related to it. A nonspecific complex III consists of the Ku autoantigen, an abundant 70- to 80-kDa protein complex in HeLa nuclear extracts. By cotransfection experiments, we demonstrate that in F9 teratocarcinoma cells, the grp78 promoter can be transactivated by the phosphorylated CREB or when the CREB-transfected cells are treated with the calcium ionophore A23187. The differential regulation of the grp78 gene by cAMP in specific cell types and tissues is discussed.
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PMID:A binding site for the cyclic adenosine 3',5'-monophosphate-response element-binding protein as a regulatory element in the grp78 promoter. 183 91

Expression of the mtHSPs (HSP60 and mtHSP70) was immunohistochemicall observed in biopsied limb muscles of genetically determined mitochondrial cytopathies (chronic progressive ophthalmoplegia 14, MELAS 4, limb girdle syndrome with the A-to-G transition at nt.3243 of tRNALeu(UUR), exertional myoglobinuria with multiple deletions of mtDNA 2, and Leber's hereditary optic neuropathy 2). mtHSP 70 and HSP 60 were strongly localized at ragged-red fibers. In strongly succinate dehydrogenase-reactive vessels of MELAS, mtHSP70 was expressed. GRP78 was expressed in the cytoplasmic body, which is often observed in this disorder. The present data suggest that expression of mtHSPs may reflect increased numbers of mitochondria, an impairment of assembly of mitochondrial proteins encoded by the genomic DNA and abnormal mitochondrial DNA, and/or an impaired mitochondrial function due to recurrent oxygen radical attacks against mitochondria.
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PMID:[Immunostaining of mitochondrial heat shock proteins (mtHSPs) in skeletal muscle fibers of mitochondrial cytopathy]. 868 94

Phospholipase D (PLD) plays a crucial role in the regulation of some cellular processes, including autophagy and apoptosis. Accumulation of protein in the endoplasmic reticulum (ER) lumen causes ER stress. Although ER stress is a principal cause of apoptosis and autophagy, the relationship between PLD activity and ER stress remains unclear. Protein transport from the ER to the Golgi apparatus is conducted by coat complex II (COPII) transport vesicles. Here, we demonstrated that inhibition of PLD1 activity or PLD1 knockdown suppressed COPII vesicle transport in normal rat kidney (NRK) cells. COPII vesicle coat proteins are composed of Sar1 as well as Sec23/24 and Sec13/31 complexes. For COPII vesicle formation on the ER membrane, Sar1, Sec23/24, and Sec13/31 are sequentially recruited from the cytosol to the ER membrane. Using a cell-free COPII coat protein recruitment assay, we demonstrated that inhibition of PLD1 activity suppressed Sec13/31 recruitment from the cytosol to the ER membrane in COPII vesicle formation. PLD1 knockdown in NRK cells was associated with increased expression of the ER stress marker GRP78 and apoptosis. Taken together, these results suggest that PLD1 activity regulates COPII vesicle transport from the ER to the Golgi apparatus by regulating Sec13/31 recruitment from the cytosol to the ER membrane during COPII vesicle formation.
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PMID:Inhibition of PLD1 activity causes ER stress via regulation of COPII vesicle formation. 2864 1