MYL6B Human

What is MYL6B and what is its fundamental role in human cells?

MYL6B is a 208 amino acid protein that functions as an essential light chain of myosin. It does not bind calcium and associates with myosin II heavy chains to form non-muscle myosin II holoenzymes (NMII) . These molecular complexes are critical for cellular contractility and cytoskeletal dynamics.

Each mammalian nonmuscle myosin-2 heavy chain associates with one essential light chain (encoded by either MYL6 or MYL6B) and one regulatory light chain (encoded by MYL9, MYL12A, or MYL12B) . This tripartite structure forms the functional unit that participates in numerous cellular processes including cytokinesis, cell shape maintenance, and specialized functions such as secretion and capping .

How does MYL6B interact with other myosin-related proteins?

MYL6B participates in a complex network of protein-protein interactions that collectively orchestrate cytoskeletal dynamics. According to STRING interaction network data, MYL6B has strong predicted functional partnerships with:

• MYL12A (score: 0.984): Myosin regulatory light chain 12A, which plays crucial roles in regulating contractile activity

• MYH10 (score: 0.980): Myosin-10, involved in cytokinesis and cell shape determination

• MYL6 (score: 0.977): A paralog that also functions as a myosin essential light chain

• MYL9 (score: 0.976): Myosin regulatory light polypeptide 9, important in contractile regulation

• MYH9 (score: 0.974): Myosin-9, which has distinct but complementary functions to MYH10

During cell spreading, MYL6B as part of myosin complexes plays an important role in cytoskeleton reorganization and focal contact formation, particularly in the central part but not the margins of spreading cells .

What is known about tissue-specific expression of MYL6B?

While detailed tissue-specific expression data is not fully presented in the search results, MYL6B expression is known to be carefully regulated across different tissues. The Human Protein Atlas contains comprehensive information about MYL6B expression patterns across human tissues and cells .

Studies indicate that nonmuscle myosin-2 paralogs and their splice variants are expressed simultaneously in most cells in a strictly regulated manner . This suggests that MYL6B expression is likely to follow tissue-specific patterns that correlate with the functional requirements for nonmuscle myosin II activity in different cell types.

How does MYL6B regulate the MDM2-p53 pathway?

MYL6B has been identified as a novel MDM2 and p53 binding protein through immunoprecipitation and mass spectrometry analysis . The protein facilitates the binding of MDM2 to p53, consequently promoting p53 ubiquitination and degradation . This mechanism reveals a previously unrecognized role for MYL6B in regulating cell cycle control and apoptosis through the critical MDM2-p53 axis.

Importantly, this regulatory function occurs as part of intact NMII holoenzymes, as inhibiting the ATPase activity of myosin II heavy chain largely blocked MYL6B's effect on p53 . This finding establishes a novel link between cytoskeletal elements and tumor suppressor pathways, potentially explaining one mechanism through which cytoskeletal dysregulation contributes to oncogenesis.

What is the relationship between MYL6B and epithelial-mesenchymal transition (EMT)?

EMT is a critical process in cancer progression that enables epithelial cells to acquire mesenchymal properties, enhancing their migratory and invasive capabilities. Research on rectal adenocarcinoma has demonstrated that MYL6B knockdown leads to increased expression of E-cadherin (an epithelial marker) and decreased expression of N-cadherin and Vimentin (mesenchymal markers) .

This finding suggests that MYL6B positively regulates EMT, potentially by influencing cytoskeletal reorganization required for the morphological and functional changes during EMT. The mechanistic details of how MYL6B modulates EMT-related protein expression remain to be fully elucidated, but this relationship provides important insights into how cytoskeletal proteins may contribute to cancer metastasis.

How does MYL6B contribute to cellular contractility and cytoskeletal dynamics?

As an essential component of nonmuscle myosin II complexes, MYL6B contributes to cellular contractility by helping form the functional myosin units that interact with F-actin in an ATP-dependent manner . These interactions drive cytoplasmic contractility essential for processes like cytokinesis, cell motility, and maintenance of cell shape.

Nonmuscle myosin-2 holoenzymes containing MYL6B oligomerize into discrete ~310 nm long bipolar filaments that can be visualized as puncta inside cells . The specific contribution of MYL6B to myosin function relates to its role as an essential light chain, providing structural support to the myosin heavy chain and potentially influencing the kinetics of the myosin ATPase cycle.

What evidence links MYL6B to cancer development and progression?

Multiple lines of evidence implicate MYL6B in cancer biology:

• Hepatocellular carcinoma (HCC):

  • MYL6B is overexpressed in HCC tissues

  • Its expression correlates with poor patient prognosis

  • Knockout of MYL6B dramatically suppresses clonogenic ability and increases apoptosis in HCC cell lines

  • MYL6B promotes p53 degradation through enhancing MDM2-mediated ubiquitination

• Rectal adenocarcinoma:

  • Overexpression observed in tumor tissues compared to normal tissues

  • Expression correlates with poor patient outcomes

  • Functional experiments show MYL6B knockdown inhibits proliferation, migration, and invasion while promoting apoptosis

These findings collectively identify MYL6B as a putative tumor driver gene that promotes cancer progression through multiple mechanisms, including p53 suppression and enhancement of cell proliferation and invasion.

What are the molecular mechanisms by which MYL6B promotes tumor growth?

MYL6B appears to promote tumor growth through several complementary mechanisms:

• p53 pathway regulation: MYL6B facilitates MDM2-mediated ubiquitination and degradation of p53, potentially suppressing p53-dependent tumor suppression mechanisms like cell cycle arrest and apoptosis .

• Enhanced proliferation: Knockdown studies demonstrate that MYL6B supports cancer cell proliferation, as its reduction significantly inhibits growth in rectal adenocarcinoma cell lines .

• Invasion and migration: MYL6B positively regulates cancer cell invasion and migration capabilities, potentially through its effects on cytoskeletal dynamics and EMT .

• Apoptosis resistance: Reduction of MYL6B expression promotes apoptosis in cancer cells, suggesting it normally functions to protect cancer cells from programmed cell death .

These diverse mechanisms position MYL6B as a multifunctional contributor to cancer biology that influences both cellular behaviors and molecular signaling pathways.

How might MYL6B serve as a prognostic biomarker or therapeutic target?

Based on current research, MYL6B shows promise as both a prognostic biomarker and potential therapeutic target:

As a prognostic biomarker:

• Overexpression correlates with poor prognosis in both HCC and rectal adenocarcinoma

• The consistency of this association across different cancer types suggests MYL6B may be a broader indicator of cancer aggressiveness

As a therapeutic target:

• Experimental knockdown demonstrates significant anti-cancer effects including reduced proliferation, migration, and invasion while increasing apoptosis

• The involvement of MYL6B in the p53 pathway suggests targeting it might help restore normal p53 function in tumors

• Its role in cytoskeletal dynamics and cell motility suggests targeting MYL6B might reduce metastatic potential

Development of specific inhibitors targeting MYL6B function or its interactions with MDM2/p53 could represent a novel therapeutic strategy worth exploring in preclinical models.

What techniques are most effective for studying MYL6B expression patterns?

Several complementary approaches have proven effective for analyzing MYL6B expression:

• Bioinformatic analysis:

  • Mining public databases (Oncomine, GEPIA, UALCAN-TCGA) to assess expression levels across tissues and disease states

  • Correlation analyses between expression and clinical outcomes

• Molecular techniques:

  • Quantitative RT-PCR for mRNA expression analysis

  • Western blotting for protein-level assessment

  • Immunohistochemistry for tissue expression patterns and subcellular localization

• Single-cell approaches:

  • Single-cell RNA sequencing for cell-type specific expression patterns

  • In situ hybridization for spatial context within tissues

For comprehensive assessment, researchers should combine multiple approaches to understand both the quantity and localization of MYL6B expression in their experimental system.

What are the optimal methods for manipulating MYL6B function in experimental settings?

Researchers have successfully employed several strategies to manipulate MYL6B function:

• Genetic approaches:

  • siRNA-mediated knockdown for transient reduction in expression

  • CRISPR-Cas9 gene editing for stable knockout models

  • Overexpression systems using plasmid transfection

• Protein function modulation:

  • Inhibition of myosin II ATPase activity blocks MYL6B effects on p53 degradation

  • Targeted disruption of protein-protein interactions (e.g., MYL6B-MDM2 interaction)

• Experimental readouts:

  • Cell proliferation assays (e.g., CCK-8)

  • Migration and invasion assays (Transwell)

  • Apoptosis assessment via flow cytometry

  • Clone formation assays

  • Co-immunoprecipitation for interaction studies

The choice of method should be guided by the specific research question, with consideration for the potential functional redundancy between MYL6B and related proteins like MYL6.

What challenges exist in studying MYL6B interactions and function?

Researchers face several methodological challenges when investigating MYL6B:

• Functional redundancy: MYL6B shares high homology with MYL6, potentially enabling compensatory mechanisms that may mask phenotypes in single-gene manipulation studies .

• Complex interaction network: MYL6B participates in extensive protein-protein interactions within the myosin complex and potentially beyond, complicating the interpretation of experimental results .

• Technical limitations: When using fluorescent protein-tagged constructs to study myosin light chains, the presence of tags can affect protein function. For example, GFP-tagged regulatory light chains show reduced enzymatic activity compared to unmodified versions .

• Context dependency: MYL6B functions may vary significantly between cell types and physiological states, necessitating careful consideration of experimental models.

• Off-target effects: Many non-myosin binding partners of myosin light chains have been described, creating potential for confounding effects when manipulating MYL6B expression .

Addressing these challenges requires carefully designed experiments with appropriate controls and complementary approaches to validate findings.

How does MYL6B function differ from its paralog MYL6?

While both MYL6 and MYL6B function as essential light chains of myosin, emerging research suggests they may have distinct roles. Both proteins do not bind calcium and associate with myosin heavy chains , but their differential expression patterns and potential functional specialization remain areas requiring further investigation.

Future research should address:

• Comparative binding affinities to different myosin heavy chains

• Tissue-specific expression patterns

• Differential roles in cancer and other disease states

• Potential unique binding partners beyond the myosin complex

What is the structural basis for MYL6B's interaction with MDM2 and p53?

The discovery that MYL6B facilitates MDM2-p53 interaction raises important structural biology questions . Research is needed to determine:

• The specific domains or residues of MYL6B involved in binding MDM2 and p53

• Whether these interactions are direct or mediated through other proteins

• The three-dimensional structure of the MYL6B-MDM2-p53 complex

• How these interactions are regulated in physiological and pathological conditions

Structural studies using techniques like X-ray crystallography, cryo-electron microscopy, or nuclear magnetic resonance spectroscopy would provide valuable insights into these questions.

How might targeting MYL6B affect normal cellular functions?

Before pursuing MYL6B as a therapeutic target, researchers must understand the potential consequences of inhibiting its function in normal cells. Key questions include:

• The extent of MYL6B's role in normal cellular mechanics versus cancer-specific functions

• Whether compensatory mechanisms exist that might mitigate effects of MYL6B inhibition in normal cells

• Tissue-specific dependencies on MYL6B function

• The therapeutic window between anti-cancer efficacy and potential toxicity

Careful studies in appropriate model systems are needed to address these important considerations for translational development.