HSP27

Official Full Name

heat shock protein family B (small) member 1

Organism

Homo sapiens

GeneID

3315

Background

This gene encodes a member of the small heat shock protein (HSP20) family of proteins. In response to environmental stress, the encoded protein translocates from the cytoplasm to the nucleus and functions as a molecular chaperone that promotes the correct folding of other proteins. This protein plays an important role in the differentiation of a wide variety of cell types. Expression of this gene is correlated with poor clinical outcome in multiple human cancers, and the encoded protein may promote cancer cell proliferation and metastasis, while protecting cancer cells from apoptosis. Mutations in this gene have been identified in human patients with Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. [provided by RefSeq, Aug 2017]

Synonyms

CMT2F; HMN2B; HMND3; HSP27; HSP28; Hsp25; SRP27; HS.76067; HEL-S-102;

Bio Chemical Class

mRNA target

Protein Sequence

MTERRVPFSLLRGPSWDPFRDWYPHSRLFDQAFGLPRLPEEWSQWLGGSSWPGYVRPLPPAAIESPAVAAPAYSRALSRQLSSGVSEIRHTADRWRVSLDVNHFAPDELTVKTKDGVVEITGKHEERQDEHGYISRCFTRKYTLPPGVDPTQVSSSLSPEGTLTVEAPMPKLATQSNEITIPVTFESRAQLGGPEAAKSDETAAK

Open

Disease

Bladder cancer, Breast cancer, Lung cancer, Ovarian cancer, Prostate cancer, Rheumatoid arthritis

Approved Drug

Clinical Trial Drug

1 +

Discontinued Drug

1 +

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Detailed Information

Heat shock protein 27 (HSP27) is a key member of the small heat shock protein (sHSP) family. This protein is highly conserved and plays critical roles in cellular processes such as cell proliferation, differentiation, and stress resistance. HSP27 functions primarily as a molecular chaperone, assisting in the proper folding of proteins and protecting cells from damage induced by various stressors. The protein is found throughout the body, and its activity is largely regulated by phosphorylation at specific serine residues. These phosphorylation events lead to the formation of oligomers, which are central to HSP27's functional roles. The protein's involvement in numerous diseases, particularly cancer and neurodegenerative conditions, has spurred interest in it as a potential therapeutic target.

Structure and Regulation of HSP27

HSP27 is characterized by a highly conserved alpha-crystallin domain, which is common to all sHSPs. The protein's activity is modulated by phosphorylation at three specific serine residues (Ser15, Ser78, and Ser82). The phosphorylation of HSP27 influences its oligomeric state, which is essential for its chaperone activity. In its dephosphorylated state, HSP27 forms large oligomers that exhibit chaperonin activity, while phosphorylation favors the formation of small oligomers that bind to microfilaments, stabilizing them. This dynamic regulation is controlled by the mitogen-activated protein kinase-activated protein kinase (MAPKAPK) family, which is activated by upstream kinases, including p38 MAPK. The reversible phosphorylation and oligomerization of HSP27 are crucial for maintaining cellular proteostasis, particularly under stressful conditions.

Figure 1. The structural changes in HSP27, show its transition from large to small oligomers upon phosphorylation by MAPKAPK 2/3. (Somu P, et al., 2024)

HSP27 in Cancer

HSP27 plays a significant role in cancer biology, where its overexpression is often linked to poor prognosis, tumorigenesis, metastasis, and resistance to chemotherapy. The phosphorylation patterns of HSP27 differ between cancerous and normal cells, which has led to the protein being considered a potential tumor biomarker. In cancers such as meningioma, the accumulation of HSP27 correlates with increased resistance to chemotherapy, anti-apoptotic activity, and enhanced cell survival. The protein's ability to protect cells from apoptosis—especially in response to cytotoxic drugs, oxidative stress, and hyperthermia—has made it a focal point in cancer research. This anti-apoptotic function, mediated by the formation of large oligomers, contributes to the resistance of cancer cells to treatment.

In addition to its role in preventing cell death, HSP27's influence on various molecular pathways, such as Akt and NF-kB, further highlights its importance in cancer progression. The protein's ability to regulate apoptosis and protect cells from cellular stress makes it an attractive target for therapeutic interventions aimed at overcoming chemotherapy resistance.

Therapeutic Targeting of HSP27 in Cancer

Given its crucial role in cancer progression, HSP27 has become a promising target for therapeutic strategies. Several approaches are being explored to inhibit its function and enhance the effectiveness of cancer treatments. These strategies include the use of small molecules, protein aptamers, and antisense oligonucleotides (ASOs).

1. Small Molecule Inhibitors: Small molecules that bind to HSP27 and prevent its oligomerization or phosphorylation are being developed as potential cancer therapies. For example, RP101 (Brivudine) has been shown to bind to HSP27 and inhibit its function. In preclinical studies, RP101 has enhanced the effectiveness of chemotherapy agents like gemcitabine and has improved the survival of pancreatic cancer patients in clinical trials. Similarly, quercetin, a bioflavonoid, has been found to inhibit HSP27 activity by regulating its stability. Quercetin also acts as a chemosensitizer, enhancing the cytotoxic effects of chemotherapy drugs.

2. Protein Aptamers: Protein aptamers are small peptides designed to bind to specific proteins, disrupting their function. Peptides such as PA11 and PA50 have been shown to inhibit HSP27 oligomerization and dimerization. These aptamers interfere with HSP27's role in cell survival and apoptosis regulation, making them effective in combination with other therapies. Studies have demonstrated that these peptide aptamers can enhance the sensitivity of cancer cells to radiation and chemotherapy, offering a promising route for cancer treatment.

3. Antisense Oligonucleotides (ASOs): ASOs are designed to bind to mRNA and prevent the translation of specific proteins. The ASO OGX-427 targets HSP27 mRNA, inhibiting its expression and reducing HSP27 levels in cancer cells. Clinical studies have shown that OGX-427 when combined with chemotherapy, can extend the survival of patients with metastatic pancreatic cancer and improve the efficacy of radiation therapy in certain cancers.

HSP27 in Neurodegenerative Diseases

Beyond its role in cancer, HSP27 is also implicated in several neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. In these conditions, HSP27 helps prevent the aggregation of misfolded proteins, a hallmark of many neurodegenerative diseases. By stabilizing proteins and preventing their accumulation, HSP27 may offer a protective mechanism against the development and progression of these diseases. Its potential as a therapeutic target for neurodegenerative disorders is an area of ongoing research.

References:

Somu P, Mohanty S, Basavegowda N, et al. The Interplay between Heat Shock Proteins and Cancer Pathogenesis: A Novel Strategy for Cancer Therapeutics. Cancers (Basel). 2024;16(3):638.
Shan R, Liu N, Yan Y, et al. Apoptosis, autophagy and atherosclerosis: Relationships and the role of Hsp27. Pharmacol Res. 2021;166:105169.
Ramani S, Park S. HSP27 role in cardioprotection by modulating chemotherapeutic doxorubicin-induced cell death. J Mol Med (Berl). 2021;99(6):771-784.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry