immune system or suppress immunity. they can promote th17, th1, th2 or treg responses depending on antigen-presenting cells. as a result, the clinical use of heat-shock proteins is both in cancer treatment (boosting an immune response) and treatment of autoimmune diseases (suppress of immunity). lens alpha crystallin (α4- crystallin) or hspb4 is involved in the development of lens in zebrafish as it is expressed in response to heat shock in the zebrafish embryo in its developmental stages. clinical significance hsf-1 heat shock factor 1 (hsf1) is a transcription factor that is involved in the general maintenance and upregulation of hsp70 protein expression. recently it was discovered that hsf1 is a powerful multifaceted modifier of carcinogenesis. hsf1 knockout mice show significantly decreased incidence of skin tumor after topical application of dmba (7,12-dimethylbenzanthracene), a mutagen. moreover, hsf1 inhibition by a potent rna aptamer attenuates mitogenic (mapk) signaling and induces cancer cell apoptosis. diabetes mellitus diabetes mellitus (dm) is a immune-disease characterized by the presence of hyperglycemia. typically these symptoms are brought about by insulin deficiency. however, there have been many recent articles alluding to a correlation between hsp70, in some cases hsp60, and dm. another recent article discovered the ratio of ehsp70 and ihsp70 could have an effect on dm, leading to a sufficient biomarker. serum levels of hsp70 have also been shown to increase over time in patients with diabetes. cancer hsp expression plays a pivotal role in cancer identification. recent discoveries have shown that high concentrations of ehsp can indicate the presence of contentious tumors. additionally, hsps have been shown to benefit oncologist in oral cancer diagnosis. using techniques such as dot immunoassay and elisa test researchers have been able to determine that hsp-specific phage antibodies could be beneficial in-vitro cancer diagnosis markers. hsps have also been shown to interact with cancer adaptations such as drug resistance, tumor cell production and lifespan, and the up-regulation and down-regulation of oncomirs. applications cancer vaccines given their role in presentation, hsps are useful as immunologic adjuvants (damps) in boosting the response to a vaccine. furthermore, some researchers speculate that hsps may be involved in binding protein fragments from dead malignant cells and presenting them to the immune system. in a recent study published by sedlacek et al., hsp was shown to effect different signaling pathways involved in carcinogenesis responses such as stat1 activation, gp96-activated macrophages, and activation of nk cells. therefore, hsps may be useful for increasing the effectiveness of cancer vaccines. also isolated hsps from tumor cells are able to act as a specific anti-tumor vaccine by themselves. tumour cells express a lot of hsps because they need to chaperone mutated and over-expressed oncogenes, tumour cells are also in a permanent stress. when we isolate hsps from a tumour, the peptide repertoire bound by hsps is somewhat a fingerprint of these particular tumour cells. application of such hsps back into patient then stimulate immune system (promotes efficient antigen presentation and act as damp) specifically against the tumor and leads to tumor regression. this immunisation is not functional against a different tumour. it was used in autologous manner in clinical studies for gp96 and hsp70, but in vitro this works for all immune-relevant hsps. anticancer therapeutics intracellular heat shock proteins are highly expressed in cancerous cells and are essential to the survival of these cell types due to presence of mutated and over-expressed oncogenes. many hsps can also promote invasiveness and metastasis formation in tumours, block apoptosis, or promote resistance to anti-cancer drugs. hence small molecule inhibitors of hsps, especially hsp90 show promise as anticancer agents. the potent hsp90 inhibitor 17-aag was in clinical trials for the treatment of several types of cancer, but for various reasons unrelated to efficacy did not go on to phase 3. hspgp96 also shows promise as an anticancer treatment and is currently in clinical trials against non-small cell lung cancer. autoimmunity treatment acting as damps, hsps can extracellularly promote autoimmune reactions leading to diseases as rheumatoid arthritis or systemic lupus erythematosus. nevertheless, it was found, that application of some hsps into patients is able to induce immune tolerance and treat autoimmune diseases. the underlying mechanism is not known. hsps (especially hsp60 and hsp70) are used in clinical studies to treat rheumatoid arthritis and type i. diabetes. current therapeutic research areas in the treatment for dm include: long-term physical exercise, hot tub therapy (htt), and alfalfa-derived hsp70 (ahsp70). hsp90 inhibitors are another possible treatment for autoimmunity, because hsp90 is necessary for proper folding of many pro-inflammatory proteins (components of pi3k, mapk and nf-kb cascades). agricultural researchers are also investigating the role of hsps in conferring stress tolerance to hybridized plants, hoping to address drought and poor soil conditions for farming. classification the principal heat-shock proteins that have chaperone activity belong to five conserved classes: hsp33, hsp60, hsp70/hsp110, hsp90, hsp100, and the small heat-shock proteins (shsps). a standard nomenclature for human hsp genes is available. approximate molecular weight (kda) prokaryotic proteins eukaryotic proteins function 10 kda groes hsp10 (hspd) co-factor of hsp60 20–30 kda grpe in humans: grpe1, grpe2 co-factor of dnak/hsp70, only for bacterial or mitochondrial/chloroplastic forms 20-30 kda hsp20 human hspb genes. eleven members in mammals including hsp27, hspb6 or hspb1 chaperones 40 kda dnaj hsp40 (dnaj*; three subfamilies in humans) co-factor of hsp70 60 kda groel, 60kda antigen hsp60 (hspe) involved in protein folding after its post-translational import to the mitochondrion/chloroplast; a chaperonin 70 kda dnak human hspa genes. includes hsp71 (hspa8), hsp72 (hspa1a), grp78 (bip, hspa5); hsx70 (hspa1b) found only in primates. hsp110 genes are derived from this superfamily and are coded hsph1 through 4. protein folding and unfolding. provides thermotolerance to cell on exposure to heat stress and protects against h2o2. also prevents protein folding during post-translational import into the mitochondria/chloroplast. hsp110 provides tolerance of extreme temperature. 90 kda htpg, c62.5 human hspc genes. includes hsp90, grp94 (hspc4) maintenance of steroid receptors and transcription factors 100 kda clpb, clpa, clpx hsp104 (clpb) unfolding of insoluble protein aggregates; co-factor of dnak/hsp70 although the most important members of each family are tabulated here, some species may express additional chaperones, co-chaperones, and heat shock proteins not listed. in addition, many of these proteins may have multiple splice variants (hsp90α and hsp90β, for instance) or conflicts of nomenclature (hsp72 is sometimes called hsp70).