Disease relevance of HSPH1

• We went on to examine hsp105 expression in various colorectal cancers and adenomas, using immunohistochemical analysis [1].
• We earlier reported that heat shock protein 105 (hsp105), which we identified by serological analyses of recombinant cDNA expression libraries (SEREX), was overexpressed in human colon and pancreatic adenocarcinoma [1].
• The 44 of 53 patients with colorectal cancers (83.0%) and only 2 of 21 (9.5%) with colorectal adenomas had an evident overexpression of hsp105, which means that overexpression of hsp105 is a late event in the colorectal adenoma-carcinoma sequence [1].
• Heating the skin in vivo resulted in an increased skin content of HSP27, 60, 72i and 90, with maximal increase at 24 h following hyperthermia, while the skin content of HSC70 and HSP110 were unchanged [2].
• DNA vaccination of HSP105 leads to tumor rejection of colorectal cancer and melanoma in mice through activation of both CD4 T cells and CD8 T cells [3].

High impact information on HSPH1

• Hsp110, an abundant heat shock protein present in essentially all mammalian tissues, has now been shown to upregulate CD1d expression in colonic tissue culture cell lines [4].
• Immunization with the hsp110-gp100 complex protected mice against subsequent challenge with human gp100-transduced B16 melanoma, which involves both CD4(+) and CD8(+) T-cell populations [5].
• No CD8(+) T cell or antibody response was detected against HSP110 [6].
• We report here that a novel benzylidene lactam compound, KNK437, dose-dependently inhibited the acquisition of thermotolerance and the induction of various HSPs including HSP105, HSP70, and HSP40 in COLO 320DM (human colon carcinoma) cells [7].
• hsp110 is one of major heat shock proteins of eukaryotic cells and is a diverged relative of the hsp70 family [8].

Biological context of HSPH1

• The deduced amino acid sequences of pBH105-1 and pBH105-2 inserts were highly homologous to mouse hsp105alpha (96%) and hamster hsp110 (92%), and to mouse hsp105beta (93%), respectively [9].
• Mammalian Hsp70 and Hsp110 proteins bind to RNA motifs involved in mRNA stability [10].
• The regulation of Hsp105 alpha function by phosphorylation may play an important role in a variety of cellular events [11].
• As a new putative function, we have previously shown that mammalian Hsp/Hsc70 as well as a distant relative, Hsp110, selectively bind certain RNA sequences via their N-terminal ATP-binding domain [12].
• Interestingly, Hsp105 alpha suppressed 70 kDa heat-shock cognate protein (Hsc70)-mediated protein folding, whereas the phosphorylation of Hsp105 alpha at Ser(509) abolished the inhibitory activity of Hsp105 alpha in vitro [11].

Anatomical context of HSPH1

• Indirect immunofluorescence analysis with anti-Hsp105 and anti-alpha-tubulin antibodies indicated that Hsp105alpha was colocalized with microtubules [13].
• Within the cerebral hemispheres, hsp110 is present in neurons in all regions including the cerebral cortex, the hippocampus, the thalamus and the hypothalamus [14].
• In contrast, in the cerebellum, the Purkinje cells are the major hsp110 containing cells while the more abundant granule cells show little if any hsp110 labeling [14].
• On the other hand, hsp105 was evidently overexpressed only in the testis in human adult normal tissues [1].
• During immunohistochemical studies, we discovered that overexpression of hsp105 occurred not only in cases of colorectal and pancreatic adenocarcinoma, but also thyroid, esophageal, breast, and bladder carcinoma and islet cell tumor, gastric malignant lymphoma, pheochromocytoma, and seminoma [1].

Associations of HSPH1 with chemical compounds

• The fundamental point is that Hsp110 is found in conjunction with Hsp70 in the cytoplasm (and nucleus) and Grp170 is found in conjunction with78 in tha ER in every eucaryotic cell examined from yeast to humans [15].
• In dispersed cells of the whole mouse embryo on the 11th day of development, heat shock proteins (hsp73 and hsp105) were induced by a heat shock or by exposure to sodium arsenite, but not by exposure to cadmium chloride [16].
• Here, we established HeLa cells that overexpress either Hsp105alpha or Hsp105beta by removing doxycycline and examined how Hsp105 modifies staurosporine (STS)-induced apoptosis in HeLa cells [17].
• The 170 kDa glucose regulated stress protein is a large HSP70-, HSP110-like protein of the endoplasmic reticulum [18].
• Similar to Hsp70 proteins ATP binding and hydrolysis induced conformational rearrangements in both Hsp110 proteins as detected by tryptophane fluorescence [19].

Other interactions of HSPH1

• Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain [20].
• The Hsp110 family must therefore be considered an essential component of Hsp70 chaperone biology in the eukaryotic cell [21].
• This would strongly argue that Hsp110 Grp170 exhibit functions in eucaryotes not effectively performed by Hsp70s or Grp78, respectively [15].
• The 110-kDa heat shock protein (hsp110) has long been recognized as one of the primary heat shock proteins in mammalian cells [22].
• Cathepsin E and hsp105 were identified as previously unknown predictors of survival in lung AC [23].

Analytical, diagnostic and therapeutic context of HSPH1

• The present report describes a combined Northern and Western blot analysis of hsp110 expression in various regions of mouse and human brain [14].
• Thus, hsp105 is a useful marker of a variety of human tumors and hsp105 may prove to be a target molecule for designing anti-tumor immunotherapy [1].
• Furthermore, a rabbit antibody was raised against recombinant human hsp105alpha, and immunofluorescence study also confirmed that hsp105 was present in the cytoplasm but was not found in the nucleoli of mammalian cells under both nonstressed and stressed conditions [9].
• Molecular cloning, expression and localization of human 105 kDa heat shock protein, hsp105 [9].
• Peptide mapping analysis of Hsp105 alpha phosphorylated by CK2 and in vitro phosphorylation experiments using various deletion and substitution mutants of Hsp105 alpha revealed that Hsp105 alpha is phosphorylated at Ser(509) in the beta-sheet domain [11].

References