Disease relevance of Stip1

• The cereolysin AB genes from Bacillus cereus VKM-B164 have been expressed in Bacillus anthracis strains: virulent H-7 (PXO1, PXO2), vaccine STI-1 (PXO1), 221 (without its own plasmids) [1].

High impact information on Stip1

• Because purified hsp90 and hsp70 are sufficient for some activation of GR steroid binding activity, some investigators have rejected any role for Hop in GR.hsp90 heterocomplex assembly [2].
• Here, we counter that impression by showing that all of the Hop in reticulocyte lysate is present in an hsp90.Hop.hsp70 complex with a stoichiometry of 2:1:1 [2].
• Addition of Hop or Ydj1 had no affect on the rate or magnitude of the activation of the stripped receptors, and quantitative Western blots confirmed that neither Hop or Hsp40 were present in our protein preparations or in the stripped receptors [3].
• These results suggest distinct but overlapping binding sites on hsp90 for different TPR proteins and indicate that the binding site for Hop, which is associated with hsp90 in intermediate stages of protein folding, overlaps with a site of chaperone activity [4].
• Structurally related tetratricopeptide repeat motifs in steroid receptor-associated immunophilins and the STI1 homolog, Hop, mediate the interaction with a common cellular target, hsp90 [5].

Biological context of Stip1

• Stress-inducible, murine protein mSTI1. Characterization of binding domains for heat shock proteins and in vitro phosphorylation by different kinases [6].
• The mSTI1 protein can be phosphorylated in vitro by cell cycle kinases proximal to a putative nuclear localization signal (NLS), which substantiated a predicted casein kinase II (CKII)-cdc2 kinase-NLS (CcN) motif at position 180-239 and suggested that mSTI1 might move between the cytoplasm and the nucleus under certain cell cycle conditions [7].
• The mSTI1 protein was exclusively cytoplasmic in most cells under normal conditions but was present in the nucleus of a subpopulation of cells and accumulated in the nucleus following inhibition of nuclear export (leptomycin B treatment) [7].
• 1. These data are consistent with results established with a model where OR and N-terminal half of the HR mediate the action of STI1 upon cell survival and upregulation of SOD activity [8].
• His6-STI1, but not its counterpart lacking the PrPc binding site, prevented cell death via PKA activation [9].

Anatomical context of Stip1

• STI1 was previously shown to be 2-fold up-regulated in MRC-5 fibroblasts upon viral transformation and to exist in a macromolecular complex with heat shock proteins of the HSP 70 and 90 families [6].
• PrP cooperates with STI1 to regulate SOD activity in PrP-deficient neuronal cell line [8].
• Expression of stress inducible protein 1 (Stip1) in the mouse testis [10].
• This suggests an important role for Stip1 in the ability of germ cells to survive in stress conditions including high temperatures [10].
• Both the protein and the mRNA of Stip1 were mainly found in the cytoplasm of all types of spermatogonia and spermatocytes up till zygotene, the expression decreased during late pachytene and was very weak in diplotene spermatocytes and round spermatids [10].

Associations of Stip1 with chemical compounds

• In vitro kinase assays using casein kinase II suggest serine 189 to be a likely phosphorylation site in mSTI1 [6].
• To analyze the biochemical properties of mSTI1 and the stoichiometry of the Hsc70.mSTI1.Hsp90 association, recombinant mSTI1 was produced in untagged, histidine (His)-tagged, and glutathione S-transferase (GST)-tagged forms [11].
• The expression of mouse stress inducible protein 1 (Stip1) was detected as upregulated as a result of MEHP exposure [10].
• Our results are consistent with a common tetratricopeptide repeat interaction site for Hop and steroid receptor-associated immunophilins within a discrete COOH-terminal domain of hsp90 [5].
• The 14-kDa polypeptide is relatively resistant to further digestion with trypsin, and seven tryptic peptides from other parts of RF-hsp 70 contain internal lysine and/or arginine residues (as do several tryptic peptides produced from IEF SSP 3521 and chick p60) [12].

Regulatory relationships of Stip1

• Stress-inducible protein 1 (STI1) is a specific PrPc ligand that promotes neuroprotection of retinal neurons through cAMP-dependent protein kinase A (PKA) [9].

Other interactions of Stip1

• The inhibitory peptides against PrP(C)-STI1 binding [STI1 pep.1 and PrP(113-132)] indicated toxic activity in PrP(C)-expressing cells by inhibiting SOD activity but not in Prnp(-/-) cells [8].
• By peptide-sequencing we have identified the two heat shock proteins that bind to murine STI1 (mSTI1) as HSC 70 and HSP 84/86 [6].
• Nuclear translocation of the Hsp70/Hsp90 organizing protein mSTI1 is regulated by cell cycle kinases [7].
• Binding of these proteins induced the phosphorylation/activation of the mitogen-activated protein kinase, which was essential for STI1-promoted neuritogenesis [9].
• Thus, the low InsP3 sensitivity of Ca2+ release in neuroblastoma cells can be explained by the presence of cytosolic inhibitors of Ca2+ release and include stress-induced phosphoprotein 1 [13].

Analytical, diagnostic and therapeutic context of Stip1

• Immunoprecipitation revealed that PrP(C) was associated with STI1 [8].
• His-mSTI1 was detected either as a dimer during size-exclusion-high-performance liquid chromatography (SE-HPLC) or as a monomer during Superdex 200 gel filtration chromatography [11].
• To assess the presence and localization of Stip1 in mouse testis and its potential role in stress defense, we studied the expression pattern of the Stip1 protein by immunohistochemistry and of the mRNA by in situ hybridization [10].

References