Disease relevance of Hsp110

• Apg-2 has a chaperone-like activity similar to Hsp110 and is overexpressed in hepatocellular carcinomas [1].
• Furthermore, dehydration increased inner medullary expression of Hsp110 and Osp94 [2].
• Characterization of heat shock protein 110 and glucose-regulated protein 170 as cancer vaccines and the effect of fever-range hyperthermia on vaccine activity [3].
• First, it is shown that prior vaccination with hsp110 or grp170 purified from methylcholanthrene-induced fibrosarcoma caused complete regression of the tumor [3].
• In a mouse TAMA26 Sertoli cell line, apg-1 transcripts were induced in 2 h by a temperature shift from 32 to 39 degrees C, but not by a shift from 37 to 42 degrees C, the traditional heat stress, or a shift from 32 to 42 degrees C. The heat response pattern of hsp110 expression was similar to that of apg-1 [4].

High impact information on Hsp110

• Intestinal heat shock protein 110 regulates expression of CD1d on intestinal epithelial cells [5].
• When proliferating cells are treated with actinomycin D (1 microgram/ml) for 8 h, hsp110 separates from the nucleolar phase-dense body to form a fluorescent nucleolar cap which resembles that seen in confluent cultures [6].
• A tumor-specific cytotoxic T lymphocyte response developed in the mice immunized with tumor-derived hsp110 or grp170 [3].
• We isolated a novel hsp110-related gene, apg-1, from a testis cDNA library [4].
• Thus, Osp94 is a new member of the hsp110/SSE stress protein subfamily and likely acts as a molecular chaperone [7].

Biological context of Hsp110

• Correlation of Hsp110 expression with caspase-3 and -9 during apoptosis induced by in vivo embryonic exposition to retinoic acid or irradiation in early mouse craniofacial development [8].
• To clarify the membership of Hsp110 family in humans, we isolated Apg-1 and Apg-2 cDNAs from a human testis cDNA library [9].
• The two clones contained the amino acid sequence found in the 17-kDa polypeptide fragments from HSP105 and 42 degrees C-HSP by lysylendopeptidase digestion [10].
• Assignment of the mouse Hsp25 and Hsp105 genes to the distal region of chromosome 5 by linkage analysis [11].
• We have shown that over-expression of hsp110 has no effect on CT26 tumor cell growth in vitro, and does not inhibit their anchorage-independent growth capacity [12].

Anatomical context of Hsp110

• In this study, we isolated mammalian cell lines for screening of Hsp modulators; mouse C3H10T1/2 cells stably transfected with a plasmid containing the mouse Hsp105 or human Hsp70B promoter upstream of a luciferase or beta-galactosidase reporter gene, respectively [13].
• An in vivo antibody depletion assay demonstrated that inactivated CT26-hsp110 cells elicited anti-tumor responses involving CD8(+) T cells and natural killer (NK) cells, but not CD4(+) T cells [12].
• These studies indicate that hsp110 and grp170 can be used in hsp-based cancer immunotherapy, that Ag-presenting dendritic cells can be used to mediate this therapeutic approach, and that fever-level hyperthermia can significantly enhance the vaccine efficiency of hsps [3].
• The 170 kDa glucose-regulated protein (grp170) is an endoplasmic reticulum resident protein that shares some sequence homology with both the hsp70 and hsp110 heat shock protein (hsp) families, yet is representative of a third and unique family of stress proteins [14].
• The antibody reacted only weakly to hsp 105 and 42 degrees C-hsp of human HeLa cells [15].

Associations of Hsp110 with chemical compounds

• Moreover, enhanced expression of Hsp110 and Osp94 was subsequent to induction of Hsp70 and was suppressed by inhibition of protein synthesis by cycloheximide [2].

Physical interactions of Hsp110

• Examination of two deletion mutants of hsp110 demonstrated that its peptide-binding domain is required for interaction with hsp25, but not with hsc70 [16].

Regulatory relationships of Hsp110

• H2O2 decreased expression of Osp94 while inducing levels of Hsp110 and Hsp70 message [2].

Other interactions of Hsp110

• Among the 17 genes identified were molecular chaperones, Hsp110, Hsp90B, and Hsp70-1 [1].
• Expression of the Hsp110 family members was further analyzed, and increased transcript levels of Hsp110 and Apg-2, but not Apg-1, were found in 12 and 14, respectively, of 18 HCCs [1].
• RT-PCR analysis showed Hsp110, Osp94, and Hsp70RY are ubiquitously expressed in mouse tissues [2].
• For all three models of apoptosis (physiological, retinoic-induced and irradiation-induced) HSP110 positive cells were more numerous than caspase-3 positive cells [8].
• RESULTS: Expression of HSP110, caspase-3 and caspase-9 was found in cells of well-known locations of programmed cell death [8].

Analytical, diagnostic and therapeutic context of Hsp110

• In this study, we explored the protective anti-tumor potency of mouse (self) Hsp70 or Hsp110-based DNA vaccination approach targeting a tumor-associated antigen, human papilloma virus (HPV) type 16 E7 protein [17].
• Examination of segmented nucleoli of postconfluent cells by immunoelectron microscopy reveals that hsp110 is associated with the fibrillar component of these nucleoli, the site of ribosomal DNA [6].
• In addition, hsp110 or grp170 immunization significantly extended the life span of Colon 26 tumor-bearing mice when applied after tumor transplantation [3].

References