Disease relevance of HSPB2

• Interferon-gamma downregulates Hsp27 expression and suppresses the negative regulation of cell death in oral squamous cell carcinoma lines [1].
• Therefore, Hsp27 is likely to provide a neuroprotective effect in AD and other tauopathies [2].
• During ischemia in alphaB-crystallin/HSPB2-deficient muscles, the development of contracture started earlier and reached a higher value compared to the wildtype mice [3].
• The recovery of contracture of alphaB-crystallin/HSPB2-deficient muscles was also attenuated during the simulated reperfusion period [3].
• Overexpression and abnormal modification of the stress proteins alpha B-crystallin and HSP27 in Alexander disease [4].

Psychiatry related information on HSPB2

• Dementia, gliosis and expression of the small heat shock proteins hsp27 and alpha B-crystallin in Parkinson's disease [5].

High impact information on HSPB2

• Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of Hsp27 [6].
• An upstream activator kinase phosphorylated a 40 kDa kinase (p40) upon threonine and tyrosine residues, which in turn phosphorylated a 50 kDa kinase (p50) upon threonine (and some serine) residues. p50 phosphorylated hsp27 upon serine. p40 and p50 were purified to near homogeneity [6].
• An IL-1-stimulated protein kinase cascade resulting in phosphorylation of the small heat shock protein hsp27 has been identified in KB cells [6].
• These results therefore demonstrate that Hsp27 is a heat-induced inhibitor of eIF4F-dependent mRNA translation [7].
• Hsp27 negatively regulates cell death by interacting with cytochrome c [8].

Chemical compound and disease context of HSPB2

• Previously we demonstrated that heat shock protein 27 (hsp27) overexpression confers resistance to the chemotherapeutic agent doxorubicin in MDA-MB-231 breast cancer cells [9].
• Change in the localization of heat shock protein 27 (HSP 27) in BG-1 human ovarian cancer cells following treatment by the ether lipid ET-18-OCH3 [10].
• Induction of neuronal differentiation in SMS-KCNR neuroblastoma cells using retinoic acid resulted in an increase in Hsp27 [11].
• This study was undertaken to examine estrogen receptor status in patients with hepatitis B virus infection and to analyze the expression of progesterone receptor and of a heat-shock 27,000-D protein (hsp27), both of which are estrogen regulated in estrogen target tissues [12].
• Blockade of Hsp27 overcomes Bortezomib/proteasome inhibitor PS-341 resistance in lymphoma cells [13].

Biological context of HSPB2

• The expression of HSPB2 protected the cells from heat-induced cell death [14].
• HSP27 does not affect I-kappaBalpha phosphorylation but enhances the degradation of phosphorylated I-kappaBalpha by the proteasome [15].
• Hsp27 plays a crucial role in the inhibition of apoptosis of oral SCC cells [1].
• Conversely, cells expressing a dominant-negative mutant of Hsp27, in which three serine residues (15, 78 and 82) were replaced by glycine, were hypersensitive to the effects of IFN-gamma and exhibited a typical apoptotic phenotype [1].
• Heat shock protein 27 (Hsp27) is a ubiquitously expressed member of the heat shock protein family that has been implicated in various biological functions including the response to heat shock, oxidative stress, and cytokine treatment [16].

Anatomical context of HSPB2

• Association of HSPB2, a member of the small heat shock protein family, with mitochondria [14].
• We previously identified HSPB2, a new member of the small heat shock protein family, expressed in heart and skeletal muscles [14].
• Double staining with anti-HSPB2 and various markers for cytoplasmic structures showed that HSPB2 was present in the cytosol as granules, some of which colocalized with mitochondria [14].
• These results suggest that MKBP constitutes a novel stress-responsive system independent of other known sHSPs in muscle cells and that DMPK may be involved in this system by being activated by MKBP [17].
• LY294002 suppressed the heat-induced accumulation of heat shock protein 27 (hsp27) and heat shock protein 72 (hsp72) in these cell lines [18].

Associations of HSPB2 with chemical compounds

• Induction of HSP27 nuclear immunoreactivity during stress is modulated by vitamin C [19].
• These results suggest that LY294002 inhibits anti-apoptosis signaling through hsp27 and hsp72 as well as cell survival signaling through Akt and survivin [18].
• Recently, we have identified that 27-kDa heat shock protein (HSP27) can serve as a sensitive marker of skin irritation, as exposure of human skin to sodium lauryl sulfate (SLS) both in vitro and in vivo induced relocalization of HSP27 from the cytoplasm to the cell nucleus [19].
• HSP27 and alphaB-crystallin accumulated in both soluble and, more prominently, insoluble fractions after exposure to MG-132, a proteasome inhibitor [20].
• Here we show that continued treatment of MM cells with bortezomib leads to a SCIO-469-enhanced downregulation of Hsp27 and to increased MM apoptosis [21].

Regulatory relationships of HSPB2

• Our data suggest that IFN-gamma suppresses Hsp27 expression in oral SCC cells and blocks the inhibitory effects of this molecular chaperone on apoptotic cell death [1].
• Selective antagonism of p38 MAP kinase blocked PDGF-BB-stimulated HSP 27 phosphorylation, membrane ruffling, and migration, but did not alter PDGF-BB-induced proliferation [22].
• Present data from colonic smooth muscle cells transfected with non-phospho-HSP27 mutant cDNA indicate that the absence of phospho-HSP27 inhibits acetylcholine-induced caldesmon phosphorylation [23].

Other interactions of HSPB2

• Recombinant clones overexpressing Hsp27 were more resistant to IFN-gamma-induced cell death than parent cells [1].
• Especially, the expressions of HSPB3, identified for the first time as a 17-kDa protein in this paper, and MKBP/HSPB2 are distinctly specific to muscles [24].
• Myotonic dystrophy protein kinase (DMPK)-binding protein, MKBP, has high homology with a small heat shock protein, HSP27 [25].
• Stress-induced nuclear relocalization of HSP27 was observed in excised skin exposed to SLS or UV light and in reconstructed epidermis only when the latter was generated in the absence of vitamin C. The omission of vitamin C results in an impaired barrier function [19].
• At the same concentrations (10-100 microM), they also increased basal phosphorylation of the small heat shock protein (hsp27) and prevented the IL1- and phorbol 12-myristate 13-acetate-induced increases of its phosphorylation [26].

Analytical, diagnostic and therapeutic context of HSPB2

• In addition, Northern blot analysis revealed that expression of HSPB2 mRNA is higher in slow-twitch muscle than in fast-twitch muscle, which correlates with the amounts of mitochondria present in these two types of tissue [14].
• Most interestingly, from 2D gel electrophoresis analysis, we identified that the expression of heat shock protein 27 (HSP27), known as a suppressor of poly(Q)-mediated cell death, dramatically decreased in SK-N-SH cells stably transfected with full-length mutant MJD [27].
• Western blotting analyses showed that MKBP level in rat heart rapidly increased, with a sharp peak at one week after birth (3-fold the level at the fetus), but that it rapidly decreased (1/10 of peak value at 13 weeks) [25].
• Immunofluorescence analysis revealed that exposure to proteasome inhibitors induced the formation of aggresomes in U373 MG cells, to which HSP27 and alphaB-crystallin were recruited [20].
• We describe a Western blot study measuring hsp27 levels in 425 patients and an immunohistochemistry (IHC) study analyzing 788 patients [28].

References