Disease relevance of HSP40

• Twenty-six tissue specimens of inflamed areas from patients with UC, 16 from patients with Crohn's disease (CD) and 16 endoscopically normal tissues were analysed for HSP40 expression [1].
• In patients with inactive disease, those with proctitis or left-sided colitis had higher titres of anti-HSP40 autoantibodies than those with total colitis [1].
• Autoantibodies against heat shock protein 40 (HSP40) and their clinical significance in ulcerative colitis (UC) have not been evaluated before [1].
• A significative correlation between the detection of human viruses by PCR and the values of bacteriophages of B. fragilis HSP40 in urban raw sewage was observed [2].
• Bacteroides fragilis HSP40 phages have been detected in waters with various levels of fecal contamination of human origin [3].

High impact information on HSP40

• Cysteine string protein (CSP) alpha is an abundant synaptic vesicle protein that contains a DNA-J domain characteristic of Hsp40-type cochaperones [4].
• The cluster of genes whose up-regulation was potentiated by GSH depletion included two HSPs (HSP40 and HSP70) and the AP-1 transcription factor components Fos and FosB [5].
• Such overproduction of Hap46 also resulted in enhanced expression of specific reporter gene constructs and in increased levels of mRNAs specific for hsp70 and hsp40 after temperature stress [6].
• Heat shock proteins Hsp70 and Hsp40 co-localize with the aggregates and activation of the chaperone system by geldanamycin leads to a reduction of aggregate formation [7].
• Dual function of membrane-bound heat shock protein 70 (Hsp70), Bag-4, and Hsp40: protection against radiation-induced effects and target structure for natural killer cells [8].

Chemical compound and disease context of HSP40

• Increased expression of HDJ-2 (hsp40) in carotid artery atherosclerosis: a novel heat shock protein associated with luminal stenosis and plaque ulceration [9].

Biological context of HSP40

• We analyzed two CCAAT-containing promoters, HSP70 and HSP40, with recombinant NF-Y and HSP-CBF using electrophoretic mobility shift assay, protein-protein interactions, transfections and chromatin immunoprecipitation assays (ChIP) assays [10].
• Our study suggests that autoimmunity against HSP40 may have a beneficial effect in UC patients by limiting the extent of the disease [1].
• No introns were found in the region corresponding to the human Hsp40 cDNA, and two direct repeats flank this same region [11].
• A pseudogene for the human Hsp40 gene has been characterized (psiHSP40) [11].
• The sensitivity of the nested-PCR was between 10(-1) and 10(-2) PFU for purified HSP40 phage solutions, sewage and seawater samples, and between 1 and 10 PFU for river water samples [12].

Anatomical context of HSP40

• HEDJ, an Hsp40 co-chaperone localized to the endoplasmic reticulum of human cells [13].
• The formation of these aggresomes required intact microtubules and involved the recruitment of chaperones, including Hsp40, Hsp70, and alphaB-crystallin [14].
• Eukaryotic cells possess two major ribosome-associated systems, an Hsp70/Hsp40-based chaperone system and the functionally enigmatic NAC complex, whereas prokaryotes employ the Trigger Factor chaperone [15].
• After thermal stress, Hsc70 is translocated to synapse-enriched areas of the cerebral cortex where it associates with Hsp40 to form a complex that can refold denaturated proteins [16].
• For the azide-exposed native cell line, addition of the antioxidant trolox to the medium abrogated both Hsp70/Hsp40 translocation and upregulation [17].

Associations of HSP40 with chemical compounds

• In eukaryotes, newly synthesized proteins interact co-translationally with a multitude of different ribosome-bound factors and chaperones including the conserved heterodimeric nascent polypeptide-associated complex (NAC) and a Hsp40/70-based chaperone system [18].
• Some chaperones such as Hsp40 and Hsp70 have been identified as important regulators of polyglutamine aggregation and/or cell death in neuronal cells [19].
• In addition, several heat-shock proteins (Hsp) [Hsp27 (2.78-fold), Hsp70 (3.75-fold), and Hsp40-like protein (3.21-fold)] were induced by curcumin [20].
• 17-AAG induced Hsp70 and Hsp40 in vivo as previously reported; however, its ability to induce HSPs was limited, suggesting that the HSP induction might support the degradation of mutant protein [21].
• Domain requirements of DnaJ-like (Hsp40) molecular chaperones in the activation of a steroid hormone receptor [22].

Physical interactions of HSP40

• The J-domain of Hsp40 couples ATP hydrolysis to substrate capture in Hsp70 [23].

Regulatory relationships of HSP40

• In contrast, three compounds inhibited the ability of Hsp40 to stimulate Hsp70 ATPase activity but did not affect the endogenous activity of Hsp70 [24].

Other interactions of HSP40

• Two of these agents also compromised the Hsp70/Hsp40-mediated post-translational translocation of a secreted pre-protein in vitro [24].
• Some genes induced by OS in the current study (e.g., oxygen regulated protein [ORP150] and heat shock protein [HSP40]) are better known to respond to other forms of stress [25].
• Furthermore, Cdc48 can act as a co-chaperone in the Hsc70-Hsp40 chaperone system [26].

Analytical, diagnostic and therapeutic context of HSP40

• The expression of six SPs--MT, HSP25/27, HSP40, HSP60, HSP70, and HSP90--was then determined by ELISA [27].
• Immunohistochemistry showed that 17 out of 26 specimens from UC patients, one specimen from a CD patient and one normal tissue specimen were positive for HSP40 [1].
• Translation of mRNA for some expressed genes, including HSP70 and HSP40, was corroborated by Western blotting [28].
• Similar results were obtained by overexpression of Hsp70 and Hsp40 in a separate cell culture model of HD [29].
• This acetylation site mutant exhibits ligand-dependent 1C2 immunoreactivity, forms aggregates that co-localize with Hsp40, Hsp70, and the ubiquitin-protein isopeptide ligase (E3) ubiquitin ligase carboxyl terminus of Hsc70-interacting protein (CHIP), and inhibits proteasome function [30].

References