Affinage

CNN1

Calponin-1 · UniProt P51911

Length
297 aa
Mass
33.2 kDa
Annotated
2026-06-09
16 papers in source corpus 11 papers cited in narrative 11 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CNN1 (calponin 1) is a smooth muscle-specific actin filament-associated protein that inhibits actin-activated myosin ATPase activity and stabilizes the actin cytoskeleton to fine-tune smooth muscle contractility, with its activity modulated by phosphorylation (PMID:26970176). Beyond this contractile role, the available corpus characterizes CNN1 predominantly as a downstream effector whose expression is set by multiple regulatory layers and whose restoration suppresses malignant and pathological cell behaviors. CNN1 abundance is constrained transcriptionally by lncRNA LINC00337, which recruits DNMT1 to hypermethylate the CNN1 promoter (PMID:33328585), and post-transcriptionally by miRNAs targeting its 3'UTR, including miR-106b-5p (PMID:31986487) and miR-330, the latter sequestered by the ceRNA lncRNA MEG3 (PMID:38240701); CNN1 protein is further stabilized against degradation by the deubiquitinase USP48 (PMID:40513941). When restored, CNN1 acts through several effector pathways: suppression of Rho/ROCK1 signaling to limit migration and invasion (PMID:31986487), and inhibition of ERK1/2 phosphorylation to reduce CXCL1/CXCL2 release in a cardioprotective context (PMID:40513941). CNN1 also participates in an epigenetic axis with Kdm6a/UTX governing endothelial senescence and SASP secretion after spinal cord injury (PMID:38528029).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2016 High

    Established the core biochemical identity of CNN1 as a smooth-muscle actin-binding protein that restrains myosin ATPase and is phosphoregulated, defining its baseline contractile function.

    Evidence Review consolidating decades of in vitro actin-activated myosin ATPase assays, actin-binding and phosphorylation studies, and expression analyses

    PMID:26970176

    Open questions at the time
    • Does not address CNN1 function outside smooth muscle
    • Does not connect contractile biochemistry to transcriptional/cancer regulation
  2. 2020 Medium

    Showed CNN1 is a direct miRNA target whose loss activates a pro-metastatic signaling cascade, framing CNN1 as a suppressor of migration/invasion.

    Evidence Dual-luciferase 3'UTR assay, overexpression/knockdown, Rho/ROCK1 inhibition, and in vivo lung metastasis assay in breast cancer cells

    PMID:31986487

    Open questions at the time
    • Direct CNN1-Rho/ROCK1 biochemical link not shown
    • miR-106b-5p effects may involve other targets
  3. 2020 Medium

    Identified an epigenetic mechanism (lncRNA-directed DNMT1 promoter methylation) that silences CNN1, linking its loss to tumor angiogenesis and proliferation.

    Evidence Bisulfite/methylation-specific PCR, DNMT1 recruitment assays, and xenograft/tube formation assays in colorectal cancer

    PMID:33328585

    Open questions at the time
    • Mechanism linking CNN1 loss to VEGF induction not defined
    • Single lab
  4. 2021 Low

    Proposed that restored CNN1 suppresses EMT and Wnt/β-catenin signaling via a TIMP2/DKK1 axis, extending its tumor-suppressive reach.

    Evidence Overexpression with wound-healing, Transwell, RT-qPCR and western blot in lung squamous carcinoma

    PMID:34178128

    Open questions at the time
    • No direct TIMP2-CNN1 binding demonstrated; pathway placement inferred from expression changes
    • Overexpression-only design
  5. 2022 Low

    Linked CNN1 to metabolic reprogramming by showing its overexpression downregulates HIF-1α-driven glycolysis in bladder cancer.

    Evidence Overexpression with metabolic flux assays, proliferation/invasion assays, and xenografts

    PMID:35903683

    Open questions at the time
    • No biochemical mechanism connecting CNN1 to HIF-1α established
    • Single lab, overexpression-driven
  6. 2024 Medium

    Placed CNN1 within an epigenetic axis with Kdm6a/UTX controlling endothelial senescence, broadening its role beyond cancer into injury/inflammation biology.

    Evidence Endothelial-specific UTX knockout mice, UTX-CNN1 binding/ChIP assays, SASP profiling, and functional recovery after spinal cord injury

    PMID:38528029

    Open questions at the time
    • Directionality of UTX effect on CNN1 expression not fully resolved
    • Functional contribution of CNN1 itself to senescence not isolated from UTX
  7. 2024 Low

    Demonstrated a non-smooth-muscle role for CNN1 in satellite-cell proliferation, differentiation, and lipid accumulation during myogenesis.

    Evidence siRNA knockdown in primary chicken breast muscle satellite cells with proliferation/differentiation/lipid assays

    PMID:38669818

    Open questions at the time
    • No molecular mechanism defined
    • Single knockdown approach in non-mammalian cells
  8. 2024 Medium

    Confirmed direct MEG3-miR-330 interaction that relieves miRNA suppression of CNN1, reinforcing a ceRNA layer controlling CNN1 levels.

    Evidence Dual-luciferase and RIP assays plus miRNA-mimic rescue in breast cancer cells

    PMID:38240701

    Open questions at the time
    • CNN1 downstream effectors in this context not mapped
    • Single lab
  9. 2025 Medium

    Identified USP48 as a deubiquitinase that stabilizes CNN1 protein, defining a post-translational control point with cardioprotective consequences via ERK1/2-CXCL1/2 suppression.

    Evidence Proteomics, cardiac-specific USP48 KO/OE mice, CNN1-silencing rescue, RNA-seq, and CXCL1/2 neutralization

    PMID:40513941

    Open questions at the time
    • Direct USP48-CNN1 deubiquitination biochemistry not fully reconstituted
    • Mechanism by which CNN1 represses ERK1/2 unclear
  10. 2025 Low

    Connected CNN1 to ferroptosis induction through a p53/SLC7A11 axis in colorectal cancer.

    Evidence CNN1 overexpression, p53 reporter and SLC7A11 promoter-binding assays, ferroptosis and rescue assays

    PMID:40602187

    Open questions at the time
    • No direct CNN1-p53 biochemical interaction shown
    • Pathway placement inferred from expression/rescue data
  11. 2026 Low

    Reported that histone lactylation upregulates CNN1 to drive autophagy, cell-cycle arrest, and docetaxel resistance in castration-resistant prostate cancer, casting CNN1 context-dependently as pro-survival.

    Evidence CRPC tissue analysis, lactate inhibition, CNN1 OE/KO in cell lines and xenografts, cell cycle and autophagy assays

    PMID:42129130

    Open questions at the time
    • Epigenetic-CNN1 link correlative; no direct lactylation writer-promoter interaction shown
    • Mechanism linking CNN1 to autophagy/arrest undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CNN1's defined actin/myosin biochemistry mechanistically couples to the diverse signaling pathways (Rho/ROCK1, ERK1/2, HIF-1α, p53/SLC7A11, Wnt) attributed to it remains unresolved.
  • No direct biochemical link established between CNN1's cytoskeletal activity and downstream signaling effectors
  • Most non-muscle pathway claims rest on single-lab overexpression/correlative data

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 1 GO:0098772 molecular function regulator activity 1
Localization
GO:0005856 cytoskeleton 1
Pathway
R-HSA-397014 Muscle contraction 1
Partners
KDM6AUSP48

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 CNN1 (calponin 1) is an actin filament-associated protein that inhibits actin-activated myosin ATPase activity and stabilizes the actin cytoskeleton; it is specifically expressed in smooth muscle cells and fine-tunes smooth muscle contractility. Phosphorylation regulates calponin function. Review synthesizing three decades of biochemical assays (actin-activated myosin ATPase assays, actin-binding experiments, phosphorylation studies) and cell-type expression analyses Gene High 26970176
2020 miR-106b-5p directly binds the 3'UTR of CNN1 mRNA (confirmed by dual-luciferase assay), suppressing CNN1 expression and activating the Rho/ROCK1 signaling pathway, thereby promoting breast cancer cell migration, invasion, and lung metastasis in vivo. Dual-luciferase reporter assay, transcript half-life assay, CNN1 overexpression/knockdown in cell lines, Rho/ROCK1 inhibition assay, in vivo lung metastasis assay Aging Medium 31986487
2020 The lncRNA LINC00337 recruits DNMT1 to the CNN1 promoter region, causing hypermethylation and transcriptional suppression of CNN1 in colorectal cancer; CNN1 suppression promotes tumor angiogenesis (elevated VEGF, microvascular density) and cell proliferation/invasion. Bisulfite sequencing PCR (BSP), methylation-specific PCR (MSP), loss- and gain-of-function experiments in vitro and in nude mouse xenograft models, tube formation assay Cancer gene therapy Medium 33328585
2021 CNN1 overexpression in lung squamous cell carcinoma cells activates TIMP2 expression, which in turn upregulates DKK1 to inhibit the Wnt/β-catenin/c-myc signaling pathway, resulting in suppressed invasion, migration, and epithelial-to-mesenchymal transition (reduced MMP2, MMP9, N-cadherin, SLUG; preserved E-cadherin). Transient transfection overexpression, wound healing assay, Transwell invasion assay, RT-qPCR, western blotting, immunofluorescence Experimental and therapeutic medicine Low 34178128
2022 CNN1 overexpression in bladder cancer cells decreases protein levels of HIF-1α and its downstream glycolysis effectors (GLUT1, PKM2, LDHA, PDK1), suppressing glucose absorption, lactate secretion, ATP production, and inhibiting tumor proliferation and invasion in vitro and in vivo. CNN1 overexpression in bladder cancer cells, CCK8 proliferation assay, Transwell invasion/migration assay, metabolic flux assays (glucose, lactate, ATP), western blotting, nude mouse xenograft with IHC Frontiers in oncology Low 35903683
2024 Kdm6a (UTX) forms an epigenetic regulatory axis by binding to CNN1, orchestrating trauma-induced spinal cord microvascular endothelial cell (SCMEC) senescence and SASP secretion; UTX deletion in endothelial cells protects against senescence, reduces proinflammatory SASP factors, and promotes neurological recovery after spinal cord injury. Endothelial cell-specific UTX knockout mouse model, ChIP/binding assays demonstrating UTX–CNN1 interaction, SASP cytokine profiling, neurological functional recovery assessment, senolytic drug delivery experiments Bone research Medium 38528029
2025 USP48, a ubiquitin-specific protease, directly stabilizes CNN1 protein (preventing its degradation); the USP48/CNN1 axis inhibits ERK1/2 phosphorylation and thereby suppresses CXCL1 and CXCL2 release, conferring cardioprotection against diabetes-aggravated myocardial ischemia/reperfusion injury. Proteomics, cardiac-specific USP48 KO and overexpression in mice, CNN1 silencing rescue experiments, RNA sequencing, western blotting for ERK1/2 activation, CXCL1/2 neutralizing antibody blockade Metabolism: clinical and experimental Medium 40513941
2024 CNN1 knockdown in chicken breast muscle satellite cells reduces proliferation and differentiation and decreases lipid accumulation during differentiation, demonstrating a functional role for CNN1 in satellite cell-mediated skeletal muscle growth. siRNA-mediated CNN1 knockdown in primary satellite cells, proliferation and differentiation assays, lipid accumulation assays Poultry science Low 38669818
2024 lncRNA MEG3 acts as a competing endogenous RNA (ceRNA) by directly binding miR-330 (confirmed by dual-luciferase and RIP assays), preventing miR-330-mediated suppression of CNN1; restoration of miR-330 on top of MEG3 overexpression reduces CNN1 expression and reverses the tumor-suppressive effects of MEG3 in breast cancer cells. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP), miRNA mimic transfection rescue experiments, cell viability, migration, invasion, and apoptosis assays Aging Medium 38240701
2025 CNN1 overexpression activates p53 signaling, which in turn directly binds the SLC7A11 promoter to suppress its transcription; reduced SLC7A11 induces ferroptosis in colorectal cancer cells. CNN1 overexpression (UTMD-assisted transfection), p53 pathway reporter assays, promoter-binding analysis for p53–SLC7A11, ferroptosis assays, rescue experiments Biochemical and biophysical research communications Low 40602187
2026 Histone lactylation (H3K18la, H4K12la) upregulates CNN1 expression in castration-resistant prostate cancer; elevated CNN1 promotes autophagy and G0/G1 cell cycle arrest, contributing to docetaxel resistance. Inhibition of CNN1 reverses these effects, and in vivo CNN1 overexpression restores tumor growth under lactate inhibition. Clinical CRPC tissue analysis, lactate inhibition (2-DG/oxamate), CNN1 OE/KO in CRPC cell lines and xenograft mouse models, cell cycle analysis, autophagy assays Cell death discovery Low 42129130

Source papers

Stage 0 corpus · 16 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Calponin isoforms CNN1, CNN2 and CNN3: Regulators for actin cytoskeleton functions in smooth muscle and non-muscle cells. Gene 150 26970176
2012 Cnn1 inhibits the interactions between the KMN complexes of the yeast kinetochore. Nature cell biology 90 22561345
2020 miR-106b-5p contributes to the lung metastasis of breast cancer via targeting CNN1 and regulating Rho/ROCK1 pathway. Aging 73 31986487
2020 LINC00337 promotes tumor angiogenesis in colorectal cancer by recruiting DNMT1, which suppresses the expression of CNN1. Cancer gene therapy 29 33328585
2021 CNN1 regulates the DKK1/Wnt/β-catenin/c-myc signaling pathway by activating TIMP2 to inhibit the invasion, migration and EMT of lung squamous cell carcinoma cells. Experimental and therapeutic medicine 22 34178128
2020 The Structural Basis for Kinetochore Stabilization by Cnn1/CENP-T. Current biology : CB 16 32679099
2022 CNN1 Represses Bladder Cancer Progression and Metabolic Reprogramming by Modulating HIF-1α Signaling Pathway. Frontiers in oncology 14 35903683
2015 The Mps1 kinase modulates the recruitment and activity of Cnn1(CENP-T) at Saccharomyces cerevisiae kinetochores. Genetics 14 25716979
2024 Kdm6a-CNN1 axis orchestrates epigenetic control of trauma-induced spinal cord microvascular endothelial cell senescence to balance neuroinflammation for improved neurological repair. Bone research 10 38528029
2022 1,4-Naphthoquinone (CNN1) Induces Apoptosis through DNA Damage and Promotes Upregulation of H2AFX in Leukemia Multidrug Resistant Cell Line. International journal of molecular sciences 10 35897681
2005 Direct proteomic mapping of Streptomyces Luteogriseus Strain 103 and cnn1 and insights into antibiotic biosynthesis. Journal of proteome research 8 16335944
2024 Long non-coding RNA MEG3 acts as a suppressor in breast cancer by regulating miR-330/CNN1. Aging 4 38240701
2024 Research Note: Chicken breast muscle satellite cell function: effect of expression of CNN1 and PHRF1. Poultry science 4 38669818
2025 USP48 protects against myocardial ischemia-reperfusion injury by stabilizing and upregulating CNN1 in type 1 diabetes mice. Metabolism: clinical and experimental 2 40513941
2025 Ultrasound-targeted microbubble destruction mediated upregulation of CNN1 induces ferroptosis in colorectal cancer cells by regulating p53-related SLC7A11 expression. Biochemical and biophysical research communications 1 40602187
2026 Histone lactylation modification promotes docetaxel resistance and tumor progression through CNN1-Mediated autophagy and cell cycle arrest in Castration-resistant prostate cancer. Cell death discovery 0 42129130

Missed literature

Know a paper Affinage missed for CNN1? Flag it for the maintainers and the community.

No submissions yet.