MCL1 Antibodies

Structure of MCL1

MCL1 is a protein with a molecular weight of approximately 37.4 kDa. Its actual weight varies depending on different splicing variants, with longer isomers (such as McL1-l) having a larger molecular weight.

The MCL1 protein belongs to the BCL-2 family, and its structure contains four BH domains (BH1-BH4) specific to the BCL-2 family. These domains form a hydrophobic pocket through α -helical bundles. The core of this protein lies in its ability to bind to BH3-only proteins (such as BIM and PUMA). A special N-terminal region determines the rate at which it is ubiquitinated and degraded, which endows MCL1 with a unique short-lifetime characteristic to respond rapidly to cellular signals. A key α -helix is directly involved in regulating its conformation, exposing its BH3-binding groove in the "activated" state, thereby performing its anti-apoptotic function.

Fig. 1 MCL1 differentially regulates hematopoietic cell survival and differentiation.¹

Key structural properties of MCL1:

• Contains BH1, BH2, BH3, BH4 four characteristics of domain structure
• Hydrophobic grooves are formed for binding pro-apoptotic proteins
• Has the unique N control area control protein stability
• Maintain the three-dimensional conformation through the α -helical beam

Functions of MCL1

The core function of the MCL1 gene is to regulate apoptosis to maintain cell survival. However, it is also involved in a variety of cellular processes, including metabolic adaptation, lymphocyte homeostasis and tumorigenesis.

The mechanism of action of MCL1 protein depends on its dynamic binding to pro-apoptotic partners. Its activity is precisely regulated by various post-translational modifications such as phosphorylation and ubiquitination, which enables it to rapidly respond to intracellular and extracellular signals and determine the life and death of cells.

Applications of MCL1 and MCL1 Antibody in Literature

1. Widden, Hayley, et al. "MCL1 binds and negatively regulates the transcriptional function of tumor suppressor p73." Cell Death & Disease 11.11 (2020): 946. https://doi.org/10.1038/s41419-020-03068-7

This study reveals a novel mechanism by which the anti-apoptotic protein MCL1 directly inhibits the transcriptional activity of p73 through its reverse BH3 domain. This localization not only clarifies the function of MCL1 in DNA damage response and cell cycle regulation, but also provides a theoretical basis for the combined application of MCL1 inhibitors and platinum-based chemotherapy.

2. Fu, Dechen, et al. "MCL1 nuclear translocation induces chemoresistance in colorectal carcinoma." Cell Death & Disease 13.1 (2022): 63. https://doi.org/10.1038/s41419-021-04334-y

In p53-deficient colorectal cancer, studies have found that DNA damage chemotherapy can induce nuclear translocation of MCL1, which interacts with proteins such as enolase through its unique loop domain, generating non-classical chemotherapy resistance. This move unexpectedly exposed the dependence of cancer cells on Bcl-xL, providing a new therapeutic strategy for the combined use of chemotherapy and Bcl-xL inhibitors.

3. Pratelli, Giovanni, et al. "MCL1 inhibition overcomes the aggressiveness features of triple-negative breast cancer MDA-MB-231 cells." International journal of molecular sciences 24.13 (2023): 11149. https://doi.org/10.3390/ijms241311149

Research has found that in triple-negative breast cancer, the use of BH3 mimic A-1210477 to inhibit MCL1 not only induces nest-loss apoptosis but also effectively weakens the invasion and metastasis ability of cancer cells. The mechanisms include disrupting adhesion plaque signaling, down-regulating matrix metalloproteinases, and reversing epithelial-mesenchymal transition and dry characteristics, revealing the key role of MCL1 in inhibiting malignant tumor progression.

4. Jacob, Maureen, et al. "Increased MCL1 dependency leads to new applications of BH3-mimetics in drug-resistant neuroblastoma." British journal of cancer 129.10 (2023): 1667-1678. https://doi.org/10.1038/s41416-023-02430-8

Research has found that in chemotherapy-resistant neuroblastoma, survival is highly dependent on the MCL1 protein. Based on this, combining BH3 mimics targeting MCL1 with NK cell-based immunotherapy offers a promising new strategy for the treatment of recurrent neuroblastoma.

5. Duan, Lei, et al. "Novel markers of MCL1 inhibitor sensitivity in triple-negative breast cancer cells." Journal of Biological Chemistry 300.6 (2024). https://doi.org/10.1016/j.jbc.2024.107375

This study identified a predictive marker composed of four genes to address the issue of inconsistent efficacy of MCL1 inhibitors in triple-negative breast cancer. This characteristic spectrum can not only predict the sensitivity of MCL1 inhibitors, but also the small molecule inhibitors in its pathway can overcome drug resistance, providing a new strategy for tumor stratification and combination therapy.

Creative Biolabs: MCL1 Antibodies for Research

Creative Biolabs specializes in the production of high-quality MCL1 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom MCL1 Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our MCL1 antibodies, custom preparations, or technical support, contact us at email.