Recombinant Human CDC37 protein(Met1-Val378), GST-tagged

• Cat.No.: CDC37-3072H
• Product Overview: Recombinant Human CDC37 (NP_008996.1) (Met 1-Val 378) was expressed in Insect Cells, fused with the GST tag at the C-terminus.

Specification

• Species: Human
• Source: Insect Cells
• Tag: GST
• Protein Length: Met1-Val378
• Form: Lyophilized from sterile 50mM Tris, 100mM NaCl, 0.5mM GSH, 0.5mM PMSF, 10% glycerol, pH 7.4. Normally 5 % - 8 % trehalose, mannitol and 0.01% Tween80 are added as protectants before lyophilization.
• Molecular Mass: The recombinant human CDC37/GST chimera consists of 603 amino acids and has a predicted a molecular mass of 70.7 kDa as estimated in SDS-PAGE under reducing conditions.
• Endotoxin: < 1.0 EU per μg of the protein as determined by the LAL method
• Purity: > 85 % as determined by SDS-PAGE
• Storage: Samples are stable for up to twelve months from date of receipt at -20°C to -80°C. Store it under sterile conditions at -20°C to -80°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles.
• Reconstitution: It is recommended that sterile water be added to the vial to prepare a stock solution of 0.2 ug/ul. Centrifuge the vial at 4°C before opening to recover the entire contents.

Gene Information

• Gene Name: CDC37 cell division cycle 37 homolog (S. cerevisiae) [ Homo sapiens ]
• Official Symbol: CDC37
• Synonyms: CDC37; cell division cycle 37 homolog (S. cerevisiae); CDC37 (cell division cycle 37, S. cerevisiae, homolog) , CDC37 cell division cycle 37 homolog (S. cerevisiae); hsp90 co-chaperone Cdc37; CDC37 (cell division cycle 37; S. cerevisiae; homolog); CDC37 cell division cycle 37 homolog; Hsp90 co chaperone Cdc37; P50CDC37; hsp90 chaperone protein kinase-targeting subunit; CDC37 (cell division cycle 37, S. cerevisiae, homolog)
• Gene ID: 11140
• mRNA Refseq: NM_007065
• Protein Refseq: NP_008996
• MIM: 605065
• UniProt ID: Q16543

Case Study

Case 1: Li K, et al. Andrology. 2021

Heat shock protein 90 (Hsp90) is involved in protein changes during sperm capacitation, but the details aren't well understood. This study looked into how Hsp90 interacts with its partner protein, Cdc37, in human sperm. It was found that Hsp90 pairs up with Cdc37. During sperm capacitation, inhibitors like H-89 and Go6983 reduced Hsp90’s phosphorylation on certain amino acids. Additionally, using 17-AAG lowered the phosphorylation at a key Src protein site and decreased threonine phosphorylation levels with both 17-AAG and geldanamycin. This suggests a complex role of Hsp90 in human sperm capacitation.

Fig1. Immunoblot analysis of the Cdc37 protein in human spermatozoa.

Fig2. Hsp90 detection in sperm lysate by immunoblotting (IB) and immunoprecipitation (IP) of 350 µg total protein with antibodies against Hsp90 and Cdc37.

Case 2: Liu W, et al. Biochemistry. 2015

Protein kinases need chaperones to fold properly, and in higher organisms, CDC37 helps guide them to HSP90. This process involves CDC37’s unstructured N-terminal domain, which undergoes a change when phosphorylated at Ser13 by CK2, shifting CDC37 into a more compact form. This change is not due to the phosphate group itself but happens because Ser13 loses its original traits. The N-terminal tail seems to act as an internal chaperone for CDC37, helping it switch states and influencing how it binds clients and interacts with HSP90.

Fig1. Estimate of phosphorylation efficiency of endogenous CDC37 in MCF7 cells.

Fig2. Increase in compactness requires the removal of Ser-like properties.

Application

CDC37 is crucial for helping protein kinases mature and stay stable by working together with HSP90. Researchers use recombinant CDC37 to explore its interactions with proteins like HSP90 and certain kinases, including CDK4/6, Raf-1, and Src. New studies indicate that small-molecule inhibitors targeting CDC37 can break apart the CDC37-HSP90 partnership, disrupting the maturation process of kinases. In terms of cancer, CDC37's connection with HSP90 is key to how tumors grow and survive, making it a possible target for cancer treatments. These inhibitors have shown promising effects across different tumors, emphasizing CDC37's importance in cancer research. CDC37 also plays a part in studying neurodegenerative diseases by interacting with tau protein, which affects its stability and aggregation. Inhibiting CDC37 can reduce tau accumulation, suggesting a potential therapeutic angle for conditions like Alzheimer's disease. This protein is essential for drug screening and developing new cancer treatments, as recombinant CDC37 can be employed in high-throughput screening for inhibitors of the HSP90-CDC37 interaction. A specific small-molecule inhibitor, DDO-6079, has demonstrated good anti-tumor effects through an allosteric mechanism that prevents the formation of the HSP90-CDC37 complex, showcasing its potential as a therapy. Recombinant CDC37 has industrial applications, produced using genetic engineering in insect cells or E. coli to achieve high purity and low endotoxin levels, making it suitable for research and diagnostic purposes. It's valuable in creating specific antibodies for CDC37 and plays a role in understanding cell proliferation, signaling, and protein stability. Overall, recombinant CDC37 offers extensive applications in cancer biology, neurodegenerative disease research, and drug development, serving as a pivotal tool for exploring cellular signaling and crafting new treatment strategies.

Fig1. Schematic representation of Hsp90/Cdc37 regulated major kinases and proteins linked to neurodegenerative diseases. (Liam Gracia, 2019)