Disease relevance of DNAJB1

• Finally, we extend these studies to a PC12 neural model of polygln toxicity in which we demonstrate that overexpression of HDJ-1 suppresses polygln aggregation with a parallel decrease in toxicity [1].
• Up to date hundreds of HSP40 proteins derived from various species ranging from Escherichia coli to homo sapiens have been identified [2].
• Here we report that expression of Gam1, a protein encoded by the avian virus CELO (ref. 11), elevates and relocalizes hsp70 and hsp40 [3].
• Unlike the general perception of the role of the cellular chaperone proteins in assisting viral protein folding and thus enhancing virus replication, ectopic expression of Hdj1 and hTid1 suppressed replication of HBV in transfected human hepatoma cells [4].
• Turnover of hepatitis B virus X protein is facilitated by Hdj1, a human Hsp40/DnaJ protein [5].

Psychiatry related information on DNAJB1

• Effects of heat shock, heat shock protein 40 (HDJ-2), and proteasome inhibition on protein aggregation in cellular models of Huntington's disease [6].
• In addition, we found the altered expression of LIM and HSPF1 both in the brains and lymphoblastoid cells in bipolar disorder [7].

High impact information on DNAJB1

• Whereas the main role of the HSP70/HSP40 chaperone system is to minimize aggregation of newly synthesized proteins, the HSP60 chaperones also facilitate the actual folding process by providing a secluded environment for individual folding molecules and may also promote the unfolding and refolding of misfolded intermediates [8].
• Thus, an essential function of Gam1 during virus replication is to activate host heat-shock responses with hsp40 as a primary target [3].
• Posttranslational protein transport into the yeast endoplasmic reticulum (ER) involves the so-called Sec complex in the membrane, comprising a similar Sec61p subcomplex, the putative signal peptide receptor subcomplex, and the heat shock protein 40-type subunit, Sec63p, plus a luminal heat shock protein 70 [9].
• (iii) Purified, recombinant hsp40 protein inhibited P58IPK in an identical in vitro assay [10].
• Loss of expression of a new member of the DNAJ protein family confers resistance to chemotherapeutic agents used in the treatment of ovarian cancer [11].

Biological context of DNAJB1

• Nucleotide sequence identity between hsp40 and HDJ1 (another human DnaJ homologue) is more than 98%, suggesting that these two proteins are the same gene product [12].
• In this report, we purified the hsp40 in HeLa cells, using modified two-dimensional gel electrophoresis, and determined the amino terminal amino acid sequence of this protein [13].
• In vivo footprinting and promoter analysis revealed that the HSEs in 5' upstream region of human Hsp40 gene were composed of eight contiguous (A/G)GAAN motifs and were essential for heat shock response [14].
• Analysis of Hsp40 transcripts by 5' and 3' RACE suggested that they have different 3' ends, and primer extension studies revealed that the major transcription initiation site was localized 47 bp upstream of the ATG translation initiation codon [14].
• There are several families of chaperones; those most involved in protein folding are the 40-kDa heat shock protein (HSP40; DnaJ), 60-kDa heat shock protein (HSP60; GroEL), and 70-kDa heat shock protein (HSP70; DnaK) families [8].

Anatomical context of DNAJB1

• We have previously reported the altered expressions of HSPF1 and LIM in the lymphoblastoid cell lines (LCLs) derived from Japanese patients with bipolar disorder (bipolar I disorder) [15].
• Here we demonstrate that Hsc70, Hsp40, and the 20 S proteasome activator PA28 are the effective components in reticulocyte lysate [16].
• Two other Hsp90 inhibitors, 17-allylamino-17-demethoxygeldanamycin (17-AAG) and radicicol, and pyrrolidine dithiocarbamate induced robust expression of Hsp70 and Hsp40 in motor neurons, but at cytotoxic concentrations [17].
• Heat shock and HDJ-1 both ameliorated MPP(+)-induced cytotoxicity by maintaining the mitochondrial membrane potential and reducing reactive oxygen species (ROS) [18].
• 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 [19].

Associations of DNAJB1 with chemical compounds

• When purified infectious virus was incubated with soluble hsc70 in the presence of the cochaperone hsp40 and ATP and then pelleted through a sucrose cushion, the recovered virus had lost 60% of its infectivity, even though hsc70 was not detected in the pellet fraction [20].
• HSP70 accumulated in the Triton-soluble fraction, whereas HSP90 and HDJ1 proteins accumulated in the Triton-insoluble fraction [21].
• Hsp70 and Hsp40 attenuate formation of spherical and annular polyglutamine oligomers by partitioning monomer [22].

Physical interactions of DNAJB1

• HDJC9, a novel human type C DnaJ/HSP40 member interacts with and cochaperones HSP70 through the J domain [2].
• (iv) Finally, we demonstrate that hsp40 directly complexes with P58IPK, in vitro, suggesting the inhibition occurs through a direct interaction [10].
• Immunoprecipitation analysis indicated that hsp40 forms a complex with the non-aggregated form of hsc70 and denatured luciferase [23].

Regulatory relationships of DNAJB1

• Hsp70 and Hsp40 improve neurite outgrowth and suppress intracytoplasmic aggregate formation in cultured neuronal cells expressing mutant SOD1 [24].
• Site-directed mutagenesis of one of these, the J domain (by which Hsp40-class chaperones bind to and activate specific Hsp70 partners) abolishes the capacity of glsA to rescue mutants [25].
• To achieve a high yield of recombinant human CYP3A4 in Escherichia coli, the CYP3A4 encoding gene was co-expressed with the chaperone HDJ-1, under the control of an inducible tac promoter in a bicistronic format [26].
• To achieve high yield of recombinant human CYP1A2 in Escherichia coli, the CYP1A2 encoding gene was co-expressed with the chaperone HDJ-1 under the control of an inducible tac promoter in bicistronic format [27].

Other interactions of DNAJB1

• The deduced amino acid sequence of HLJ1 has an 84% homology (69% identity) with that of HDJ-1 isolated from human placenta [28].
• The structure supports the hypothesis that the highly conserved tripeptide could play a key role in the interaction of Hsp40 with the molecular chaperone, Hsp70 [29].
• The binding of HSP40 to PR was sustained and did not interact in the highly dynamic fashion that has been observed previously for HSP90 in this system [30].
• Furthermore, the import process is specific, saturable, and requires action of the chaperone Hsc70, the cochaperone Hsp40, and the peroxins Pex5p and Pex14p [31].
• Modulation of the chaperone activities of Hsc70/Hsp40 by Hsp105alpha and Hsp105beta [32].

Analytical, diagnostic and therapeutic context of DNAJB1

• Indirect immunofluorescence staining using an anti-hsp40 polyclonal antibody demonstrated that hsp40 was localized faintly throughout the cell in non-heat-shocked cells and was accumulated in nuclei and nucleoli in heat-shocked cells [13].
• In addition, hsp40 was co-localized with hsc70(p73) in heat-shocked HeLa cells as demonstrated by double immunofluorescence staining [33].
• Co-immunoprecipitation of hsp70 with hsp40 was dependent on the presence of ATP or unfolded protein (reduced carboxymethylated alpha-lactalbumin) [34].
• We have previously shown that hTid-1 and Hdj1, the human Hsp40/DnaJ chaperone proteins, bind the HBV core protein and inhibit viral replication in cell culture system [5].
• This study was done to determine whether the expression of heat shock protein HDJ-2 (heat shock protein 40), heat shock protein 60, and heat shock protein 70 are increased during rejection in human pulmonary allografts [35].

References