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MCL1

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

Background

The MCL1 gene is located in the 1q21.2 region of the human chromosome and encodes the myeloid cell leukemia 1 protein (MCL1), which belongs to the anti-apoptotic subfamily of the BCL-2 family. MCL1 is an integral membrane protein, with its C-terminal transmembrane region anchoring it to the mitochondrial outer membrane and its N-terminal domain exposed to the cytosol. Its molecular weight is approximately 37 kDa and it is broadly expressed across human tissues, with relatively high expression in hematopoietic tissues such as bone marrow and spleen. As a critical regulator of mitochondrial apoptosis, MCL1 binds and neutralizes pro-apoptotic BH3-only proteins such as BIM and NOXA, as well as the effector proteins BAK and BAX, thereby preventing mitochondrial outer membrane permeabilization and blocking cytochrome c release. This gene is subject to multiple regulatory mechanisms, including transcriptional control, post-translational modifications, and rapid proteasomal degradation mediated by its N-terminal PEST sequences. Phosphorylation at specific residues promotes ubiquitination and accelerates protein turnover, while caspase cleavage generates functionally distinct protein fragments. Beyond its anti-apoptotic role, a mitochondrially processed isoform of MCL1 localizes to the mitochondrial matrix, where it participates in the regulation of mitochondrial bioenergetics and cristae structure maintenance. MCL1 is frequently amplified or overexpressed in multiple cancer types, including multiple myeloma, acute myeloid leukemia, and breast cancer, where it serves as a major resistance factor against conventional chemotherapies and BCL-2-selective inhibitors such as venetoclax. Therefore, MCL1 is regarded as an important molecular target for studying apoptosis regulation, mitochondrial homeostasis, and cancer cell survival mechanisms. Its functional analysis provides valuable tools for understanding the molecular basis of apoptotic signaling and identifying approaches to overcome apoptosis-related drug resistance.

Fig.1 Schematic representation of USP13, MCL1, and their truncation mutants. (OA Literature)Fig. 1 Schematic of full-length USP13 (FL), full-length MCL1 (FL) and their deletion mutants (M1, M2, U1, U2).1

Function of MCL1 Protein: A Central Regulator of Mitochondrial Apoptosis and Cell Survival Signaling

The functional spectrum of MCL1 is extensive and is continuously expanding:

  • Regulation of mitochondrial apoptosis: MCL1 binds to and neutralizes pro-apoptotic BH3-only proteins such as BIM and NOXA, as well as the effector proteins BAK and BAX on the mitochondrial outer membrane, preventing mitochondrial outer membrane permeabilization and blocking the release of cytochrome c and other apoptogenic factors, thereby maintaining cell survival under diverse stress conditions.
  • Mitochondrial quality control and bioenergetics: A mitochondrially processed isoform of MCL1 localizes to the mitochondrial matrix, where it contributes to the regulation of mitochondrial fusion, ATP production, maintenance of membrane potential, and cristae ultrastructure organization, independent of its canonical anti-apoptotic function.
  • Regulation by post-translational modifications and protein turnover: MCL1 is a short-lived protein with a half-life of 1–3 hours, regulated through multiple mechanisms including phosphorylation-dependent ubiquitination, caspase-mediated cleavage generating functionally distinct fragments, and PEST sequence-mediated proteasomal degradation, providing a model for studying rapid protein turnover control.
  • Structural basis of protein-protein interactions: Structural studies using NMR spectroscopy and X-ray crystallography have investigated the molecular determinants of MCL1 interactions with BH3 ligands, revealing a hydrophobic binding groove with distinct electrostatic features that govern selectivity for different pro-apoptotic binding partners, providing a foundation for understanding interaction specificity within the BCL-2 family.

MCL1 Membrane Protein Product

Creative Biolabs offers a series of high-quality MCL1 membrane protein products, suitable for structural and functional research. Relying on the independently developed MemDX™ recombinant membrane protein technology platform, MCL1 proteins can be prepared through various expression systems, including virus-like particles (VLP) and in vitro prokaryotic expression systems. These rigorously validated protein products, such as MemDX™ recombinant human MCL1 membrane protein as virus-like particles and human MCL1 proteins from various expression systems, can be used in ELISA, antibody screening and identification, binding experiments, and functional research, providing reliable tools for researchers to analyze the interactions and regulatory mechanisms of MCL1.

MCL1 Protein Product

Not finding the membrane protein product you need? Contact us to start your one-stop custom service!

MCL1 Stable Cell Line Product

Constructing a robust cell model is crucial for the study of MCL1-mediated apoptosis regulation. As an anti-apoptotic BCL-2 family member that controls mitochondrial outer membrane permeabilization, the expression level and functional status of MCL1 directly affect the threshold for apoptosis initiation and cellular sensitivity to diverse death stimuli. Different genetic backgrounds, post-translational modifications, or changes in expression levels may lead to significant differences in apoptotic priming and cell survival capacity. Creative Biolabs offers customized MCL1 membrane protein stable transfection cell models, covering wild-type and various functionally characterized forms. These models stably express the target protein on the mitochondrial outer membrane, and are suitable for studies on apoptosis signaling kinetics, protein-protein interaction analysis, BH3 profiling, and assessment of cellular dependence on MCL1 for survival, providing a reliable and reproducible platform for exploring the anti-apoptotic mechanism, structure-function relationship, and mitochondrial regulatory network of MCL1. Our technology ensures mitochondrial membrane integrity and correct protein localization, facilitating your research.

MCL1 Stable Cell Line Product

Not finding the stable cell line product you need? Contact us to start your one-stop custom service!

MCL1 Recombinant Antibody Product

Creative Biolabs offers highly specific recombinant antibodies targeting MCL1, produced using advanced recombinant antibody technology. Compared to traditional antibodies, these recombinant antibodies demonstrate superior performance in terms of specificity, sensitivity, and batch-to-batch consistency. They can also be modified and labeled in various ways. Our MCL1 recombinant antibodies support a wide range of applications, including Western Blot, ELISA, flow cytometry, immunofluorescence, immunocytochemistry, immunohistochemistry, and immunoprecipitation, and can be used to detect differences in MCL1 expression levels in various tissues or cell sources, analyze its subcellular localization on the mitochondrial outer membrane, and conduct related research such as protein interaction and apoptosis signaling analysis. These antibodies provide reliable detection tools for the structural analysis, functional study of MCL1, and the investigation of its regulation in the apoptotic signaling network.

MCL1 Recombinant Antibody Product

Not finding the recombinant antibody product you need? Contact us to start your one-stop custom service!

Product Features

  • Diversified expression systems: Multiple platforms are available for recombinant protein production, including virus-like particles and prokaryotic and eukaryotic expression systems, accommodating the requirements of different research applications.
  • Broad range of experimental applications: Products can be used in ELISA, antibody screening, binding studies, protein-protein interaction analysis, Western blot, immunofluorescence, and immunohistochemistry experiments.
  • Stringent batch-to-batch consistency: Rigorous quality control protocols maintain stability across product batches, ensuring the reliability and reproducibility of experimental results.
  • Flexible customization options: Personalized customization services are supported for specific naturally occurring isoforms, tag configurations, or expression systems.

Custom MCL1 Membrane Protein and Antibody Discovery Services

In addition to the standard products, Creative Biolabs also offers professional customized services for MCL1. MCL1 has multiple functionally distinct isoforms with significant differences in apoptotic regulatory activity. These isoforms have specific requirements in aspects such as protein expression, antigen design, and functional verification. Leveraging our technology platform, we can assist you in completing the following customized projects:

  • Customized production of membrane proteins: Tailored expression using multiple expression systems, purification, and characterization for different isoforms and functional states.
  • Customized antibody development: From antigen design to antibody engineering (monoclonal, polyclonal, recombinant antibodies), supporting isoform discrimination or recognition of shared epitopes.
  • Construction of stable cell model: Generate stable cell models that express specific isoforms or functional variants, for the purpose of comparative functional studies and drug response profiling.
  • Development of the functional detection system: Design and execute experimental protocols such as apoptosis assays, protein interaction analysis, and assessment of functional differences among isoforms.

Frequently Asked Questions (FAQ)

  1. What is the main function of the MCL1 gene?

    MCL1 primarily functions as an anti-apoptotic regulator on the mitochondrial outer membrane, binding to and neutralizing pro-apoptotic BH3-only proteins such as BIM and NOXA, as well as the effector proteins BAK and BAX, to prevent mitochondrial outer membrane permeabilization and maintain cell survival. The activity and stability of this protein are significantly influenced by post-translational modifications and protein turnover, and different isoforms exhibit differences in apoptotic regulatory capacity and subcellular localization. It is an important model for studying the relationship between mitochondrial membrane protein structure and function as well as the regulatory mechanism of apoptosis.

  2. Why is MCL1 an important research target?

    MCL1 is a critical survival factor in multiple cancer types and is frequently amplified at the 1q21.2 locus in multiple myeloma, breast cancer, and other malignancies. Its overexpression is a major mechanism of resistance to conventional chemotherapies and BCL-2-selective inhibitors. Studying the regulation and function of MCL1 is helpful for a deeper understanding of the structure-function relationship of anti-apoptotic BCL-2 proteins, the molecular mechanisms of apoptosis evasion in cancer, and the identification of strategies to overcome drug resistance.

  3. Is the MCL1 product of Creative Biolabs suitable for clinical applications?

    Not applicable. All MCL1 products and services provided by Creative Biolabs are for research purposes only and cannot be used for any clinical diagnosis, prevention, treatment or cure of any disease.

  4. What types of MCL1 products does Creative Biolabs offer?

    We offer a variety of product types, including recombinant MCL1 membrane proteins, stable cell models expressing MCL1, high-quality recombinant MCL1 antibodies, as well as comprehensive customized services.

Reference
  1. Zhang, Shengzhe, et al. "Deubiquitinase USP13 dictates MCL1 stability and sensitivity to BH3 mimetic inhibitors." Nature communications 9.1 (2018): 215. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.1038/s41467-017-02693-9
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