KLHDC3 Antibody

What is KLHDC3 and what are its primary cellular functions?

KLHDC3 (Kelch domain-containing protein 3, also known as PEAS) is a protein containing six Kelch domains and a BC-box/CUL2-box motif. It functions as a substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex within the DesCEND (destruction via C-end degrons) pathway .

KLHDC3 primarily:

• Recognizes specific C-degrons located at the extreme C-terminus of target proteins

• Mediates ubiquitination and subsequent proteasomal degradation of these targets

• May be involved in meiotic recombination processes

• Plays a role in protein quality control by degrading truncated proteins

The CRL2-KLHDC3 complex specifically recognizes proteins with glycine (Gly) at the C-terminus, particularly those with C-terminal motifs such as -Arg-(Xaa)n-Arg-Gly, -Arg-(Xaa)n-Lys-Gly, and -Arg-(Xaa)n-Gln-Gly .

Which applications are KLHDC3 antibodies validated for?

KLHDC3 antibodies have been validated for multiple research applications, with variations in effectiveness depending on the specific antibody clone:

Researchers should note that optimal dilutions may vary based on the specific antibody clone and experimental conditions. A titration series is recommended when using a new antibody or testing a new experimental system .

What species reactivity has been confirmed for KLHDC3 antibodies?

Based on the available research data, KLHDC3 antibodies have demonstrated reactivity with:

• Human samples (confirmed across multiple antibody clones)

• Mouse samples (particularly in testis tissue)

• Rat samples (validated in testis tissue and selected cell lines)

This cross-species reactivity makes these antibodies valuable for comparative studies across mammalian models. When selecting an antibody for specific research purposes, check the validation data for the particular species of interest, as reactivity can vary between antibody clones.

What is the recommended protocol for immunohistochemical detection of KLHDC3?

For optimal immunohistochemical detection of KLHDC3 in tissue samples:

• Tissue preparation:

  • Use paraffin-embedded tissue sections (4-6 μm thickness)

  • Heat-mediated antigen retrieval with TE buffer pH 9.0 (preferred) or citrate buffer pH 6.0 (alternative)

• Staining protocol:

  • Block endogenous peroxidase (3% H₂O₂, 10 minutes)

  • Protein blocking (5% normal serum, 1 hour)

  • Primary antibody incubation (1:50-1:500 dilution, overnight at 4°C)

  • Secondary antibody detection (compatible with primary antibody host)

  • Chromogenic detection (DAB substrate)

  • Counterstain (hematoxylin)

• Validation controls:

  • Positive control: Human or mouse testis tissue (known to express KLHDC3)

  • Negative control: Primary antibody omission

  • Specificity control: Competitive blocking with immunogen peptide

The best results have been reported in testis tissues where KLHDC3 shows distinct nuclear and cytoplasmic staining patterns .

How does KLHDC3 contribute to the ferroptosis regulatory pathway?

KLHDC3 functions as a critical negative regulator of ferroptosis through a p14 ARF-dependent mechanism :

• Molecular mechanism:

  • KLHDC3, as part of the CRL2 E3 ubiquitin ligase complex, directly binds to p14 ARF via its Kelch domains

  • This interaction promotes p14 ARF translocation from nucleoli to nucleoplasm for degradation

  • Degradation of p14 ARF prevents its inhibitory effect on NRF2 activation

  • NRF2 upregulates SLC7A11 expression, a cystine/glutamate antiporter

  • SLC7A11 increases cystine uptake, leading to enhanced glutathione synthesis and ferroptosis resistance

• Experimental evidence:

  • KLHDC3 knockout cells show increased p14 ARF protein levels but not mRNA levels

  • KLHDC3 knockout cells are more sensitive to ferroptosis inducers (erastin and cystine deprivation)

  • This sensitivity can be reversed by p14 ARF depletion or SLC7A11 overexpression

  • In xenograft models, KLHDC3 knockout suppresses tumor growth in a partially p14 ARF-dependent manner

This pathway represents a novel regulatory mechanism for ferroptosis that is independent of p53 status, making it potentially relevant for cancer types with p53 mutations or deletions.

What structural features determine substrate specificity in KLHDC3-mediated protein degradation?

Recent structural studies have revealed key determinants of substrate specificity in KLHDC3-mediated protein degradation :

• C-terminus anchor motif:

  • KLHDC3 contains a conserved motif that anchors substrate C-termini

  • This motif is positioned in a specific blade of the β-propeller structure, creating a distinct molecular environment

  • The position differs from related proteins (KLHDC2, KLHDC10), contributing to substrate selectivity

• Pre-formed recognition pocket:

  • KLHDC3 possesses a pre-formed pocket with preference for Arg or Gln preceding a C-terminal Gly

  • This structural feature establishes the basis for recognizing specific C-degron sequences:

    • -Arg-(Xaa)n-Arg-Gly

    • -Arg-(Xaa)n-Lys-Gly

    • -Arg-(Xaa)n-Gln-Gly

• Additional interaction surfaces:

  • Non-consensus interactions mediated by:

    • C-degron binding grooves

    • Distal propeller surfaces

    • Interactions with substrate globular domains

  • These additional contacts substantially impact substrate binding affinity and ubiquitylation efficiency

How can researchers distinguish between KLHDC3 and other KLHDCX family members in experimental settings?

Distinguishing between closely related KLHDCX family members presents a significant challenge in experimental settings. Here's a methodological approach:

• Antibody-based differentiation:

  • Use antibodies targeting unique epitopes not conserved among family members

  • Validate specificity through knockout/knockdown controls for each family member

  • Employ epitope-tagging strategies when studying exogenously expressed proteins

• Functional discrimination:

  • Substrate specificity analysis:

    • KLHDC3 preferentially recognizes -Arg-(Xaa)n-Arg-Gly, -Arg-(Xaa)n-Lys-Gly, and -Arg-(Xaa)n-Gln-Gly C-degrons

    • KLHDC2 shows distinct substrate preferences compared to KLHDC3

    • KLHDC10 demonstrates greater conformational malleability for recognizing diverse C-terminal features

  • Phenotypic effects:

    • KLHDC3 depletion uniquely stabilizes p14 ARF (unlike other CRL2 adaptors)

    • KLHDC3, but not other CRL2 adaptors, promotes p14 ARF polyubiquitination

    • KLHDC3 specifically affects ferroptosis regulation and tumor growth through p14 ARF-NRF2-SLC7A11 pathway

• Expression pattern analysis:

  • Tissue-specific expression (KLHDC3 shows elevated expression in testis)

  • Subcellular localization differences

  • Cancer-specific expression patterns (KLHDC3 is overexpressed in ovarian cancer and other tumor types)

This multi-faceted approach allows researchers to reliably distinguish between closely related family members when interpreting experimental results.

What are the optimal conditions for using KLHDC3 antibodies in co-immunoprecipitation experiments?

For successful co-immunoprecipitation (co-IP) experiments investigating KLHDC3 and its interacting partners:

• Lysis buffer optimization:

  • Use BC100 buffer (20 mM Tris-Cl, pH 7.9, 100 mM NaCl, 0.2 mM EDTA, 20% glycerol) containing 0.2% Triton X-100

  • Add fresh protease inhibitors to prevent degradation

  • For nuclear proteins (like p14 ARF), include phosphatase inhibitors and DNase I

• Immunoprecipitation protocol:

  • For epitope-tagged KLHDC3:

    • Transfect cells with FLAG-HA (FH)-KLHDC3 constructs

    • Perform tandem affinity purification using anti-FLAG antibody-conjugated M2 agarose followed by anti-HA antibody-conjugated agarose

    • Elute with specific peptides (FLAG or HA peptides)

  • For endogenous KLHDC3:

    • Pre-clear lysates with protein A/G beads

    • Incubate with KLHDC3 antibody (2-5 μg) overnight at 4°C

    • Capture with protein A/G beads

    • Wash stringently (at least 4 times) with lysis buffer

    • Elute by boiling in SDS sample buffer

• Controls and validation:

  • Input control (5-10% of lysate)

  • IgG control (matching isotype)

  • Reciprocal co-IP (pull down interacting partner and probe for KLHDC3)

  • Validate specific interactions through domain deletion/mutation analysis (e.g., Kelch domain deletions abolish p14 ARF interaction)

Following this optimized protocol has enabled researchers to identify key KLHDC3 interactions, including those with CUL2, RBX1, and p14 ARF, providing insights into its biological functions.

How can researchers effectively validate KLHDC3 antibody specificity?

Rigorous validation of KLHDC3 antibody specificity is essential for reliable experimental results. A comprehensive approach includes:

• Genetic validation:

  • CRISPR-Cas9 knockout cell lines:

    • Generate guide RNAs targeting KLHDC3 gene

    • Screen knockout clones by Western blot

    • Validate by Sanger sequencing

  • siRNA/shRNA knockdown:

    • Transfect cells with KLHDC3-specific siRNAs/shRNAs

    • Confirm knockdown efficiency by qRT-PCR

    • Verify protein reduction by Western blot

• Multiple antibody comparison:

  • Use independent antibodies targeting different epitopes

  • Compare staining patterns and signal intensities

  • Concordant results from multiple antibodies increase confidence in specificity

• Recombinant protein controls:

  • Overexpression of tagged KLHDC3

  • Competition assays with immunizing peptide

  • Correlation between overexpression and signal intensity

• Protocol-specific validations:

  • For IHC/ICC: Include positive control tissues (testis) and negative control tissues

  • For Western blot: Confirm expected molecular weight (~43 kDa) and band pattern

  • For IP-MS: Validate identified interaction partners through reverse IP and functional assays

This multi-layered validation approach ensures antibody specificity and enhances reproducibility of KLHDC3-related research findings.

What role does KLHDC3 play in cancer biology, and how can KLHDC3 antibodies advance cancer research?

KLHDC3 has emerged as a potential oncogene with significant implications for cancer research:

• Expression patterns in cancer:

  • KLHDC3 mRNA is significantly overexpressed across multiple cancer types based on TCGA RNA-seq data

  • Particularly elevated in ovarian cancer compared to normal ovarian tissues

  • Expression patterns suggest a potential role in cancer development or progression

• Functional significance in cancer:

  • Regulates p14 ARF stability, a key tumor suppressor

  • Modulates cellular response to ferroptosis, a form of regulated cell death

  • KLHDC3 knockout suppresses tumor growth in xenograft models

  • These effects are partially mediated through the p14 ARF-NRF2-SLC7A11 axis

• Research applications of KLHDC3 antibodies in cancer studies:

  • Expression profiling across cancer types and correlation with clinical outcomes

  • Investigation of KLHDC3 subcellular localization in normal versus cancer cells

  • Identification of novel KLHDC3 substrates in cancer contexts

  • Development of therapeutic strategies targeting KLHDC3-mediated pathways

• Therapeutic implications:

  • Cell-penetrating p14 ARF-derived peptides can competitively inhibit KLHDC3-mediated p14 ARF degradation

  • Such peptides sensitize cancer cells to ferroptosis inducers

  • KLHDC3 inhibition might represent a novel therapeutic approach, particularly in cancers with p53 mutations

KLHDC3 antibodies thus provide crucial tools for understanding its expression, localization, and functional interactions in cancer, potentially leading to new diagnostic or therapeutic strategies.

What methodological considerations are important when studying KLHDC3's role in protein degradation pathways?

Investigating KLHDC3's function in protein degradation pathways requires careful methodological considerations:

• Substrate half-life analysis:

  • Cycloheximide chase assays:

    • Treat cells with cycloheximide to inhibit protein synthesis

    • Collect samples at defined time points

    • Analyze protein levels by Western blot

    • Compare substrate half-life in KLHDC3-depleted vs. control cells

  • Pulse-chase experiments:

    • Label newly synthesized proteins with radioactive amino acids

    • Chase with non-radioactive medium

    • Immunoprecipitate proteins of interest

    • Analyze decay rates in different cellular contexts

• Ubiquitination assays:

  • In vivo ubiquitination:

    • Co-express HA-tagged ubiquitin, substrate, and KLHDC3

    • Treat cells with proteasome inhibitors (MG132)

    • Immunoprecipitate substrate under denaturing conditions

    • Probe for ubiquitin modifications

  • In vitro reconstitution:

    • Purify recombinant CRL2-KLHDC3 complex components

    • Combine with E1, E2, ubiquitin, ATP, and substrate

    • Analyze ubiquitination by SDS-PAGE and Western blot

• Substrate recognition analysis:

  • Mutational analysis of C-terminal degrons

  • Peptide competition assays

  • Structural studies of KLHDC3-substrate complexes

• Proteasome involvement:

  • Combine KLHDC3 studies with proteasome inhibitors

  • Distinguish between ubiquitination and actual degradation

  • Control for off-target effects of inhibitors

These methodological approaches provide a comprehensive framework for investigating KLHDC3's role in protein degradation pathways and identifying its physiological substrates.

How can researchers design experiments to investigate KLHDC3's role in ferroptosis across different cell types?

To systematically investigate KLHDC3's role in ferroptosis regulation across cell types:

• Experimental model development:

  • Generate KLHDC3 knockout/knockdown in multiple cell types:

    • Cancer cell lines with varying p53 status (e.g., H1299, SKOV3, OVCAR-3, SJSA)

    • Normal cell counterparts (e.g., fibroblasts, epithelial cells)

    • Immune cells (potential non-cancer applications)

  • Create rescue models with wild-type or mutant KLHDC3 (e.g., BC-box/CUL2-box mutants)

• Ferroptosis sensitivity assessment:

  • Multiple induction methods:

    • Small molecule inducers (erastin, RSL3, sorafenib)

    • Cystine deprivation

    • GPX4 inhibition

  • Diverse readouts:

    • Cell viability assays (CCK-8, MTT)

    • Lipid peroxidation measurements (BODIPY-C11, MDA)

    • Iron chelation rescue

    • Ferroptosis inhibitor (ferrostatin-1) rescue

• Mechanistic pathway analysis:

  • Epistasis experiments:

    • p14 ARF depletion in KLHDC3 KO cells

    • NRF2 modulation

    • SLC7A11 overexpression

  • Biochemical pathway analysis:

    • Glutathione levels

    • System xc- activity

    • Transcriptional effects on ferroptosis regulators

• Therapeutic relevance assessment:

  • Combination with chemotherapeutics

  • Testing cell-penetrating peptide inhibitors

  • In vivo ferroptosis induction in xenograft models

This comprehensive experimental approach allows for a detailed understanding of KLHDC3's role in ferroptosis across different cellular contexts, potentially identifying context-dependent effects and therapeutic opportunities.

What are the best practices for multiplexed detection of KLHDC3 and its interaction partners?

For effective multiplexed detection of KLHDC3 and its interaction partners:

• Immunofluorescence co-localization:

  • Primary antibody selection:

    • Choose antibodies from different host species (e.g., rabbit anti-KLHDC3 and mouse anti-p14 ARF)

    • Validate antibodies individually before multiplexing

    • Ensure non-overlapping emission spectra

  • Detection strategy:

    • Sequential staining for closely positioned epitopes

    • Include appropriate blocking steps between primary antibodies

    • Utilize spectral unmixing for overlapping fluorophores

  • Analysis:

    • Quantify co-localization using Pearson's or Mander's coefficients

    • Conduct proper control experiments (single stains, isotype controls)

• Proximity ligation assay (PLA):

  • Particularly useful for detecting KLHDC3 interactions in situ

  • Provides higher specificity than conventional co-localization

  • Requires careful optimization of primary antibody concentrations

  • Include negative controls (non-interacting proteins)

• Multiplexed co-immunoprecipitation:

  • Sequential immunoprecipitation:

    • First IP with KLHDC3 antibody

    • Elute under mild conditions

    • Second IP with antibody against interaction partner

  • Analysis by mass spectrometry:

    • Label-free quantification

    • SILAC or TMT labeling for quantitative comparison

    • Stringent filtering against common contaminants

• Imaging mass cytometry/multiplexed ion beam imaging:

  • For tissue-level analysis of multiple proteins

  • Use metal-conjugated antibodies against KLHDC3 and interaction partners

  • Allows simultaneous detection of >40 proteins

  • Provides spatial context for protein interactions

These approaches enable comprehensive analysis of KLHDC3's interactome in different cellular contexts, advancing understanding of its diverse functions.

What are common issues encountered when using KLHDC3 antibodies, and how can they be resolved?

Researchers frequently encounter several challenges when working with KLHDC3 antibodies. Here are solutions to common issues:

• High background in Western blots:

  • Optimize blocking conditions (5% BSA often works better than milk for phospho-specific detection)

  • Increase washing duration and volume

  • Titrate primary antibody (try 1:5000-1:50000 range)

  • Use freshly prepared buffers

  • Add 0.05% Tween-20 to antibody dilution buffer

• Weak or absent signal in immunostaining:

  • Optimize antigen retrieval (TE buffer pH 9.0 recommended for KLHDC3)

  • Increase antibody concentration (start with 1:50 dilution for IHC)

  • Extend primary antibody incubation (overnight at 4°C)

  • Use signal amplification systems (HRP polymers, tyramide signal amplification)

  • Consider sample fixation method (over-fixation can mask epitopes)

• Multiple bands in Western blot:

  • Verify expected molecular weight (~43 kDa for full-length KLHDC3)

  • Include positive controls (testis tissue lysate)

  • Run KLHDC3 knockdown/knockout controls

  • Test different lysis conditions (RIPA vs. NP-40 buffers)

  • Add protease inhibitors to prevent degradation

• Low reproducibility between experiments:

  • Standardize lysate preparation and protein quantification

  • Use consistent cell culture conditions

  • Prepare antibody aliquots to avoid freeze-thaw cycles

  • Include loading controls and normalization

  • Consider lot-to-lot variations in antibodies

These troubleshooting strategies should address most common issues encountered when working with KLHDC3 antibodies across different applications.

How can researchers address issues of cross-reactivity with other KLHDCX family members?

Cross-reactivity between closely related KLHDCX family members presents a significant challenge. Here's a systematic approach to address this issue:

• Antibody selection and validation:

  • Choose antibodies raised against unique regions (non-conserved epitopes)

  • Validate using knockout/knockdown controls for all related family members

  • Perform peptide competition assays with specific immunizing peptides

  • Consider using recombinant monoclonal antibodies for increased specificity

• Specificity controls in experimental systems:

  • Include single and multiple KLHDCX family member knockdown/knockout controls

  • Perform rescue experiments with specific family members

  • Use epitope-tagged versions when studying exogenous expression

  • Verify results with multiple antibodies targeting different epitopes

• Bioinformatic sequence analysis:

  • Align sequences of KLHDCX family members

  • Identify unique regions/peptides for each family member

  • Perform epitope mapping to determine antibody binding sites

  • Use this information to predict potential cross-reactivity

• Application-specific considerations:

  • Western blot: Use high-resolution gels to separate similar molecular weight proteins

  • Immunoprecipitation: Validate with mass spectrometry to confirm identity

  • Immunostaining: Compare with known expression patterns and subcellular localization

  • Flow cytometry: Include isotype controls and blocking peptides

By implementing these strategies, researchers can minimize cross-reactivity issues and ensure specific detection of KLHDC3 in their experimental systems.

What controls should be included when studying KLHDC3-mediated protein degradation pathways?

When investigating KLHDC3-mediated protein degradation, a comprehensive set of controls should be included:

• Genetic manipulation controls:

  • KLHDC3 knockout/knockdown:

    • Complete knockout (CRISPR-Cas9)

    • Inducible knockdown (shRNA, siRNA)

    • Include scrambled/non-targeting controls

  • Other CRL2 complex components:

    • CUL2 and RBX1 depletion (positive controls)

    • Other substrate receptors (KLHDC2, KLHDC10, etc.) as specificity controls

  • Substrate manipulation:

    • C-terminal degron mutants

    • Truncation variants

    • Expression level controls

• Pharmacological controls:

  • Proteasome inhibitors:

    • MG132, bortezomib (should block KLHDC3-mediated degradation)

    • Different concentrations and time points

  • Protein synthesis inhibitors:

    • Cycloheximide (for half-life measurements)

    • Control for non-specific effects on cellular physiology

  • E1 inhibitors:

    • MLN7243/TAK-243 (should prevent ubiquitination)

    • Establish ubiquitin-dependence of degradation

• Mechanistic controls:

  • KLHDC3 domain mutants:

    • Kelch domain deletions (substrate binding)

    • BC-box/CUL2-box mutants (CRL2 complex formation)

  • Ubiquitination site mutants:

    • Lysine-to-arginine mutations in substrates

    • Identify key ubiquitination sites

• Technical controls:

  • Input samples (5-10% of lysate)

  • Loading controls (housekeeping proteins)

  • Negative controls (IgG, unrelated proteins)

  • Positive controls (known KLHDC3 substrates like p14 ARF)

What are emerging approaches for studying KLHDC3 substrate specificity and its relevance to disease?

Several cutting-edge approaches are advancing our understanding of KLHDC3 substrate specificity and disease relevance:

• Global C-terminomics approaches:

  • Terminal amine isotopic labeling of substrates (TAILS)

  • Analyzing proteome-wide changes in protein C-termini upon KLHDC3 modulation

  • C-terminal peptide enrichment coupled with mass spectrometry

  • This can identify novel physiological KLHDC3 substrates beyond known targets

• Structural biology advances:

  • Cryo-EM of CRL2-KLHDC3 complexes with substrates

  • Hydrogen-deuterium exchange mass spectrometry to map binding interfaces

  • Computational modeling of substrate recognition

  • These approaches reveal the molecular basis of substrate selectivity

• High-throughput screening platforms:

  • Peptide arrays displaying diverse C-terminal sequences

  • Reporter-based degradation assays

  • CRISPR screens for synthetic lethality with KLHDC3 deficiency

  • These methods identify determinants of substrate recognition and cellular contexts where KLHDC3 is essential

• Disease-relevant applications:

  • Patient-derived xenografts to test KLHDC3 inhibition strategies

  • Analysis of KLHDC3 expression in clinical samples correlated with outcomes

  • Investigation of KLHDC3 substrates in disease-specific contexts

  • Development of C-degron mimetics as therapeutic agents

These emerging approaches will significantly advance our understanding of KLHDC3 biology and potentially reveal new therapeutic opportunities in diseases where KLHDC3 dysfunction plays a role.

How might technical advances in antibody development improve KLHDC3 research?

Recent and emerging advances in antibody technology offer significant potential to enhance KLHDC3 research:

• Recombinant antibody technologies:

  • Single-chain variable fragments (scFvs) and nanobodies

  • Improved consistency and reduced lot-to-lot variation compared to polyclonal antibodies

  • Engineering for enhanced affinity and specificity

  • Potential for intracellular expression as "intrabodies" to target specific KLHDC3 domains

• Advanced validation technologies:

  • CRISPR-based antibody validation platforms

  • Orthogonal target verification methods

  • Automated high-throughput validation pipelines

  • These approaches ensure antibody specificity and reproducibility

• Multi-epitope targeting strategies:

  • Cocktails of antibodies targeting different KLHDC3 epitopes

  • Bispecific antibodies for enhanced specificity

  • Domain-specific antibodies to distinguish functional regions

  • These approaches provide more comprehensive information about KLHDC3 biology

• Functional antibody applications:

  • Conformation-specific antibodies to detect active/inactive KLHDC3 states

  • Antibodies that selectively block substrate binding without affecting CRL2 complex formation

  • Intracellular targeting strategies for functional manipulation

  • These tools would allow precise dissection of KLHDC3 functions

• Imaging applications:

  • Super-resolution compatible antibodies

  • Site-specific labeling for single-molecule studies

  • Proximity labeling antibody conjugates

  • These advances enable detailed analysis of KLHDC3 localization and dynamics

These technological innovations promise to address current limitations in KLHDC3 research tools and facilitate deeper understanding of its functions and disease relevance.

What is the potential significance of KLHDC3 as a therapeutic target, and how can antibody-based research advance this field?

KLHDC3 shows promising potential as a therapeutic target, particularly in cancer, with antibody-based research playing a crucial role in development:

• Therapeutic rationale:

  • KLHDC3 overexpression in multiple cancer types suggests oncogenic potential

  • KLHDC3 knockout suppresses tumor growth in xenograft models

  • KLHDC3 inhibition could restore p14 ARF tumor suppressor function

  • KLHDC3 targeting could sensitize cancer cells to ferroptosis, a novel cell death mechanism

  • CRL2-KLHDC3 represents a druggable E3 ligase complex

• Target validation through antibody research:

  • Expression profiling across normal and disease tissues

  • Correlation with clinical outcomes and treatment responses

  • Identification of patient populations likely to benefit from KLHDC3 targeting

  • Elucidation of regulatory mechanisms controlling KLHDC3 expression

• Therapeutic strategies enabled by antibody research:

  • Development of protein degradation technologies (PROTACs, molecular glues) targeting KLHDC3

  • Design of C-degron mimetics to competitively inhibit KLHDC3

  • Identification of context-dependent synthetic lethal interactions

  • Cell-penetrating peptide inhibitors derived from C-terminal degrons

• Antibody-based therapeutics:

  • Antibody-drug conjugates targeting cancer cells with high KLHDC3 expression

  • Intracellular antibody delivery strategies

  • Bispecific antibodies linking KLHDC3 to immune effector cells

  • Combination strategies with ferroptosis inducers or checkpoint inhibitors

• Biomarker development:

  • KLHDC3 expression/activity as predictive biomarker for targeted therapies

  • Monitoring treatment response through KLHDC3 substrate levels

  • Patient stratification based on KLHDC3 pathway activation