KLF12 Human
Description
KLF12 exhibits opposing roles in cancer progression, influenced by tissue type and molecular interactions:
Pro-Tumorigenic Activity
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Breast Cancer: Overexpression of KLF12 increases cell viability, colony formation, and proliferation in MCF-7 and ZR-75-30 cell lines. Knockdown reduces tumor growth .
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Immune Evasion: KLF12 inhibits galectin-1 (Gal-1), enhancing CD8+ T-cell infiltration and improving anti-PD-1 immunotherapy efficacy in murine models .
Tumor-Suppressive Activity
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Lung Cancer: KLF12 promotes anoikis (detachment-induced apoptosis). Knockdown increases metastatic survival in mouse models and correlates with poor patient prognosis .
Cardiac Remodeling and Fibrosis
KLF12 exacerbates angiotensin II (Ang II)-induced cardiac fibrosis and dysfunction:
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Upregulation in Fibrosis: KLF12 expression increases in cardiac fibroblasts (CFs) during Ang II infusion, driving collagen deposition and CF proliferation .
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Pathway Activation: Binds the Smad7 promoter, activating TGF-β/Smad3 signaling. KLF12-overexpressing mice show worsened cardiac hypertrophy (30% increase in heart weight) .
Expression Profiles and Functional Associations
KLF12 exhibits diverse expression patterns and interactions across biological systems:
Therapeutic Potential and Research Gaps
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Cancer Therapy: Targeting KLF12 could enhance immunotherapy (e.g., anti-PD-1) by reducing Gal-1 . Conversely, restoring KLF12 may counteract metastasis in lung cancer .
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Cardiac Disease: Inhibiting KLF12 in CFs attenuates Ang II-induced fibrosis, suggesting therapeutic promise .
Research Gaps:
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Context-dependent mechanisms underlying KLF12’s dual roles in cancer.
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Clinical validation of KLF12-targeted therapies in humans.
Product Specs
Q&A
Basic Research Questions
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What is KLF12 and what is its fundamental role in human biology?
KLF12 (Krüppel-like factor 12) is a member of the Kruppel-like zinc finger protein family that functions primarily as a transcription factor. It binds to specific DNA sequences in gene promoters, particularly to CACCC motifs, and can regulate gene expression either as a repressor or activator depending on cellular context . KLF12 was originally identified as a repressor of AP-2 alpha (Activator protein-2 alpha), requiring interaction with the corepressor CtBP1 for its repressive function . Research methodologies to study KLF12's fundamental role typically involve chromatin immunoprecipitation (ChIP) assays, promoter-reporter assays, and gene expression analyses following KLF12 knockdown or overexpression .
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How is KLF12 expression regulated in normal human tissues versus disease states?
KLF12 expression varies across tissue types and disease states. In normal tissues, KLF12 participates in developmental processes and homeostasis through regulated expression patterns. Methodologically, researchers assess KLF12 expression through RNA-seq, qPCR, and immunohistochemistry techniques .
In disease states, significant alterations occur:
To study regulatory mechanisms, researchers employ epigenetic profiling (methylation analysis, histone modification ChIP-seq) and transcription factor binding site analyses .
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What experimental approaches are most effective for studying KLF12's transcriptional targets?
Several complementary experimental approaches have proven effective for identifying and validating KLF12 transcriptional targets:
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ChIP-seq analysis: Allows genome-wide identification of KLF12 binding sites, particularly effective when combined with RNA-seq data to correlate binding with expression changes .
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Promoter-reporter assays: Dual-luciferase reporter systems can validate direct regulation, as demonstrated in studies of KLF12 binding to p21 and galectin-1 promoters .
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ChIP-Re-ChIP assays: These have been used to demonstrate co-occupancy of promoters by KLF12 and other factors (e.g., p53) .
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Site-directed mutagenesis of binding motifs: Critical for confirming specific KLF12 binding sites, particularly the CACCC motifs in target gene promoters .
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Integration of transcriptomics after KLF12 modulation: RNA-seq following both siRNA and shRNA-mediated KLF12 knockdown provides higher confidence in identifying genuine targets .
Challenges include antibody specificity for KLF12 ChIP applications, necessitating proper validation through knockdown and overexpression controls .
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Product Science Overview
Kruppel-Like Factor 12 (KLF12) is a member of the Kruppel-like zinc finger protein family, which plays a crucial role in regulating gene expression. This family of transcription factors is characterized by the presence of C2H2-type zinc finger motifs that bind to GC-rich regions in DNA. KLF12, in particular, is known for its ability to repress the expression of the AP-2 alpha gene by binding to a specific site in its promoter region .
KLF12 Human Recombinant is produced in Escherichia coli as a single, non-glycosylated polypeptide chain containing 425 amino acids. The recombinant protein has a molecular mass of 46.6 kDa and is fused to a 23 amino acid His-tag at the N-terminus. The protein is purified using proprietary chromatographic techniques to ensure high purity and stability .
KLF12 functions as a transcriptional repressor by interacting with corepressors such as CtBP1. It binds to the promoter regions of target genes, thereby inhibiting their transcription. This repression mechanism is vital for regulating various cellular processes, including proliferation, differentiation, and apoptosis .
KLF12 is involved in the regulation of gene expression during vertebrate development and carcinogenesis. Its ability to repress the AP-2 alpha gene, a developmentally regulated transcription factor, highlights its importance in developmental biology. Additionally, KLF12 has been implicated in various diseases, including cancer, where its dysregulation can lead to abnormal cell growth and tumor formation .
The recombinant form of KLF12 is widely used in laboratory research to study its function and regulatory mechanisms. It is particularly useful in experiments aimed at understanding gene expression, transcriptional regulation, and the role of KLF12 in disease pathogenesis. The availability of high-purity recombinant KLF12 allows researchers to conduct detailed biochemical and structural analyses, furthering our understanding of this important transcription factor .
