Affinage

CCDC34

Coiled-coil domain-containing protein 34 · UniProt Q96HJ3

Length
373 aa
Mass
43.2 kDa
Annotated
2026-04-28
51 papers in source corpus 7 papers cited in narrative 7 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCDC34 (coiled-coil domain-containing protein 34) functions as a pro-proliferative and pro-survival factor in multiple cancer types and is required for axonemal integrity in sperm flagella. In cancer cells, CCDC34 sustains MAPK (ERK, p38, JNK) and PI3K/AKT signaling to promote proliferation, suppress apoptosis, and drive epithelial-to-mesenchymal transition and invasion; it is transcriptionally activated by the homeobox factor MNX1 via direct promoter binding and acts downstream of GTP-bound RABL2A to activate p38/JNK signaling that confers sorafenib resistance (PMID:26312564, PMID:34767735, PMID:37415626). CCDC34 also promotes cancer stemness and EGFR-TKI resistance through β-catenin-mediated ATG5-dependent autophagy (PMID:39587349). A homozygous missense mutation in CCDC34 (p.A283E) causes oligoasthenoteratozoospermia with loss of outer dynein arms and disrupted axonemal ultrastructure, establishing a requirement for CCDC34 in sperm motility and flagellar assembly (PMID:38856307).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 2015 Medium

    The first functional investigation established that CCDC34, until then uncharacterized, is required for bladder cancer cell proliferation and migration through MAPK and PI3K/AKT signaling, answering whether this coiled-coil protein has signaling relevance in cancer.

    Evidence Lentiviral siRNA knockdown in bladder cancer cells with Western blot phospho-pathway analysis and nude mouse xenograft

    PMID:26312564

    Open questions at the time
    • No direct enzymatic or scaffolding activity defined for CCDC34 itself
    • Single cancer type; generalizability unknown
    • Mechanism connecting a coiled-coil protein to MAPK/AKT activation unexplained
  2. 2017 Medium

    Extended the cancer-promoting role to colorectal cancer and revealed that CCDC34 suppresses apoptosis (via BCL2/survivin) and promotes EMT (via N-cadherin/E-cadherin switch), broadening its oncogenic mechanism beyond proliferation alone.

    Evidence siRNA knockdown in SW620 cells with Western blot for apoptosis and EMT markers, invasion assays, flow cytometry

    PMID:29115580

    Open questions at the time
    • No direct protein interaction partners identified
    • EMT marker changes could be indirect consequences of proliferation effects
    • Single cell line tested
  3. 2020 Medium

    Confirmed AKT pathway engagement and EMT promotion in hepatocellular carcinoma with transcriptome-wide support and in vivo metastasis models, strengthening the case that CCDC34 is a general oncogenic factor across carcinomas.

    Evidence siRNA knockdown with RNA-seq, Western blot, xenograft and lung metastasis mouse models

    PMID:32021254

    Open questions at the time
    • Still no direct biochemical mechanism linking CCDC34 to AKT activation
    • No identification of direct binding partners in this system
  4. 2021 Medium

    Identified the first direct physical interactor of CCDC34 — GTP-bound RABL2A — and placed CCDC34 as a downstream effector that transduces RABL2A signaling to p38/JNK MAPK to confer sorafenib resistance, answering how a coiled-coil protein connects to MAPK cascades.

    Evidence Reciprocal co-immunoprecipitation, GTP/GDP-locked RABL2A mutants, epistasis by siRNA in sorafenib-resistant HCC cells, in vivo model

    PMID:34767735

    Open questions at the time
    • Whether CCDC34 directly activates kinases or acts as a scaffold/adaptor is unknown
    • RABL2A–CCDC34 interaction not confirmed by structural or biophysical methods
    • Relevance of RABL2A–CCDC34 axis outside drug resistance context untested
  5. 2023 Medium

    Demonstrated that CCDC34 is a direct transcriptional target of MNX1, establishing the first upstream regulatory mechanism for CCDC34 expression in cancer and answering why CCDC34 is upregulated in lung adenocarcinoma.

    Evidence ChIP and luciferase reporter for MNX1 binding to CCDC34 promoter; rescue of MNX1-knockdown phenotype by CCDC34 overexpression in lung adenocarcinoma cells and xenograft

    PMID:37415626

    Open questions at the time
    • Whether MNX1–CCDC34 axis operates in other tumor types is untested
    • Additional transcription factors controlling CCDC34 expression not explored
  6. 2024 Medium

    Revealed a non-cancer physiological role for CCDC34: a loss-of-function missense mutation causes oligoasthenoteratozoospermia with outer dynein arm loss, establishing CCDC34 as required for axonemal assembly in human sperm and linking it to a Mendelian fertility disorder.

    Evidence Whole-exome sequencing in a consanguineous family; transmission electron microscopy of sperm axonemes

    PMID:38856307

    Open questions at the time
    • No functional rescue experiment to confirm causality of the p.A283E variant
    • Mechanism by which CCDC34 contributes to outer dynein arm assembly is unknown
    • Single family; independent replication needed
  7. 2024 Medium

    Connected CCDC34 to cancer stemness and drug resistance by showing it drives β-catenin-mediated ATG5-dependent autophagy, providing a mechanistic basis for EGFR-TKI resistance in lung adenocarcinoma.

    Evidence Knockdown and overexpression with Western blot for β-catenin/ATG5/autophagy markers, stemness assays, EGFR-TKI combination in vitro and in vivo

    PMID:39587349

    Open questions at the time
    • How CCDC34 activates β-catenin is mechanistically undefined
    • Relationship between RABL2A–CCDC34 axis and β-catenin/autophagy axis not explored
    • No structural or biochemical data on CCDC34 protein activity

Open questions

Synthesis pass · forward-looking unresolved questions
  • The intrinsic molecular activity of CCDC34 — whether it functions as a scaffold, adaptor, or has enzymatic activity — remains unknown, as does how a single coiled-coil protein participates in both axonemal dynein arm assembly and cytoplasmic oncogenic signaling.
  • No biochemical or structural characterization of CCDC34 protein
  • No reconstitution of CCDC34 activity in vitro
  • Relationship between ciliary/flagellar and oncogenic functions unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 1
Localization
GO:0005829 cytosol 1 GO:0005929 cilium 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 1
Partners
MNX1RABL2A

Evidence

Reading pass · 7 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 CCDC34 knockdown via lentivirus-mediated siRNA suppressed bladder cancer cell proliferation and migration, induced G2/M cell cycle arrest and apoptosis in vitro, and suppressed tumor growth in nude mice. CCDC34 silencing decreased phosphorylation of MEK, ERK1/2, JNK, p38, and Akt, and reduced expression of c-Raf and c-Jun, indicating MAPK (ERK, p38, JNK) and PI3K/Akt pathways are involved in CCDC34-mediated proliferation and migration. Lentivirus-mediated siRNA knockdown, Western blot for pathway phosphorylation, in vitro proliferation/migration assays, xenograft mouse model Oncotarget Medium 26312564
2017 CCDC34 inhibition in SW620 colorectal cancer cells led to reduced cell activity, increased apoptosis, and reduced invasion; mechanistically, BCL2, survivin, N-cadherin, and MMP-9 were decreased while E-cadherin increased, indicating CCDC34 promotes CRC invasion by suppressing apoptosis and promoting epithelial-to-mesenchymal transition. siRNA knockdown, Western blot for apoptosis/invasion-associated proteins, invasion assays, flow cytometry Molecular medicine reports Medium 29115580
2020 CCDC34 knockdown in hepatocellular carcinoma cells inhibited proliferation and metastasis both in vitro and in vivo; RNA sequencing and Western blot revealed CCDC34 inhibition reduced AKT activation and suppressed epithelial-mesenchymal transition (EMT). siRNA knockdown, RNA sequencing, Western blot, xenograft and lung metastasis mouse models, CCK-8 and Transwell assays OncoTargets and therapy Medium 32021254
2021 RABL2A interacts with CCDC34 in its GTP-bound state in sorafenib-resistant HCC cells (Huh7/SR and Hep3B/SR), as confirmed by co-immunoprecipitation and immunofluorescent staining. RABL2A Q80L (GTP-locked) overexpression conferred sorafenib resistance and increased p-p38 and p-JNK, effects that were abrogated by CCDC34 depletion, placing CCDC34 downstream of active RABL2A in p38/MAPK and JNK/MAPK signaling. Co-immunoprecipitation, immunofluorescent staining, GTP/GDP-locked RABL2A mutants, siRNA knockdown, CCK-8, TUNEL, PI/Annexin V, Western blot, in vivo model DNA and cell biology Medium 34767735
2023 MNX1 directly binds to the CCDC34 promoter and transcriptionally activates CCDC34 expression, as demonstrated by luciferase reporter and chromatin immunoprecipitation assays. CCDC34 overexpression partially rescued the antitumor effect of MNX1 knockdown in lung adenocarcinoma cells, placing CCDC34 genetically downstream of MNX1. Luciferase reporter assay, chromatin immunoprecipitation (ChIP), siRNA knockdown, overexpression rescue, in vitro proliferation/migration/invasion assays, in vivo xenograft Oncology letters Medium 37415626
2024 A novel missense mutation in CCDC34 (c.848C>A, p.A283E) identified by whole-exome sequencing in a consanguineous Pakistani family with oligoasthenoteratozoospermia was associated with axonemal ultrastructural defects including lack of outer dynein arms, indicating CCDC34 plays a role in maintaining axonemal ultrastructure and assembly/stability of outer dynein arms in sperm flagella. Whole-exome sequencing, hematoxylin and eosin staining, transmission electron microscopy of sperm ultrastructure Asian journal of andrology Medium 38856307
2024 CCDC34 promotes lung adenocarcinoma stemness properties through β-catenin-mediated regulation of ATG5-induced autophagy, contributing to acquired EGFR-TKI resistance. CCDC34 knockdown synergistically inhibited tumor growth when combined with EGFR-TKIs in vitro and in vivo. WGCNA bioinformatics, siRNA knockdown, overexpression, Western blot for β-catenin/ATG5/autophagy markers, in vitro stemness assays, in vivo xenograft, drug combination assays Cancer gene therapy Medium 39587349

Source papers

Stage 0 corpus · 51 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Quantitative analysis of messenger RNA abundance for ribosomal protein L-15, cyclophilin-A, phosphoglycerokinase, beta-glucuronidase, glyceraldehyde 3-phosphate dehydrogenase, beta-actin, and histone H2A during bovine oocyte maturation and early embryogenesis in vitro. Molecular reproduction and development 109 16261607
2006 Overexpression of ribosomal protein L15 is associated with cell proliferation in gastric cancer. BMC cancer 86 16608517
2020 Lactobacillus plantarum L15 Alleviates Colitis by Inhibiting LPS-Mediated NF-κB Activation and Ameliorates DSS-Induced Gut Microbiota Dysbiosis. Frontiers in immunology 81 33123156
1987 Ribosomal proteins EL11 from Escherichia coli and L15 from Saccharomyces cerevisiae bind to the same site in both yeast 26 S and mouse 28 S rRNA. Journal of molecular biology 72 3309345
1977 Isolation of eukaryotic ribosomal proteins. Purification and characterization of 60 S ribosomal subunit proteins L3, L6, L7', L8, L10, L15, L17, L18, L19, L23', L25, L27', L28, L29, L31, L32, L34, L35, L36, L36', and L37'. The Journal of biological chemistry 68 863909
2019 Inhibition of Escherichia coli adhesion to human intestinal Caco-2 cells by probiotic candidate Lactobacillus plantarum strain L15. Microbial pathogenesis 62 31437574
2001 Detection and characterization of a bacteriocin, garviecin L1-5, produced by Lactococcus garvieae isolated from raw cow's milk. Journal of applied microbiology 62 11298239
2001 Cloning and characterization of full-length human ribosomal protein L15 cDNA which was overexpressed in esophageal cancer. Gene 57 11223259
1985 The complete primary structure of ribosomal proteins L1, L14, L15, L23, L24 and L29 from Bacillus stearothermophilus. European journal of biochemistry 50 4018095
1995 Reappearance and long-term maintenance of connexin32 in proliferated adult rat hepatocytes: use of serum-free L-15 medium supplemented with EGF and DMSO. Journal of cell science 48 7615657
1983 Characterisation of a mutant from Escherichia coli lacking protein L15 and localisation of protein L15 by immuno-electron microscopy. Molecular & general genetics : MGG 44 6197616
2019 Ribosomal Protein L15 is involved in Colon Carcinogenesis. International journal of medical sciences 42 31523176
2015 CCDC34 is up-regulated in bladder cancer and regulates bladder cancer cell proliferation, apoptosis and migration. Oncotarget 40 26312564
1991 Amino acid-rich medium (Leibovitz L-15) enhances and prolongs proliferation of primary cultured rat hepatocytes in the absence of serum. Journal of cellular physiology 37 1648566
1988 Ribosomal protein interactions in yeast. Protein L15 forms a complex with the acidic proteins. European journal of biochemistry 30 3058476
1984 Characterization of an amber mutation in the structural gene for ribosomal protein L15, which impairs the expression of the protein export gene, secY, in Escherichia coli. The EMBO journal 30 6389119
1993 Redifferentiation of proliferated rat hepatocytes cultured in L15 medium supplemented with EGF and DMSO. In vitro cellular & developmental biology. Animal 28 8407715
2017 Overexpression of CCDC34 in colorectal cancer and its involvement in tumor growth, apoptosis and invasion. Molecular medicine reports 23 29115580
1992 The genes for ribosomal protein L15 and the protein equivalent to secY in the archaebacterium Haloarcula (Halobacterium) marismortui. Biochimica et biophysica acta 22 1543743
2018 Overexpression of Coiled-Coil Domain-Containing Protein 34 (CCDC34) and its Correlation with Angiogenesis in Esophageal Squamous Cell Carcinoma. Medical science monitor : international medical journal of experimental and clinical research 20 29397026
2011 Characterization of a ribosomal protein L15 cDNA from Chironomus riparius (Diptera; Chironomidae): transcriptional regulation by cadmium and silver nanoparticles. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 19 21473924
2011 A novel interaction between interferon-inducible protein p56 and ribosomal protein L15 in gastric cancer cells. DNA and cell biology 19 21612406
2009 Functional characterization of ribosomal protein L15 from Saccharomyces cerevisiae. Current genetics 15 19184027
2024 Discovery of L15 as a novel Vif PROTAC degrader with antiviral activity against HIV-1. Bioorganic & medicinal chemistry letters 13 38996941
2022 Exopolysaccharide of Enterococcus faecium L15 promotes the osteogenic differentiation of human dental pulp stem cells via p38 MAPK pathway. Stem cell research & therapy 13 36056447
2022 In vivo evidence of the prevents DSS-induced colitis of Lactiplantibacillus plantarum L15. Frontiers in microbiology 13 36274719
2001 Storage of unprocessed G-CSF-mobilized whole blood in a modified Leibovitz's L15 medium preserves clonogenic capacity for at least 7 days. Bone marrow transplantation 13 11509932
1998 Ribosomal protein L15 as a probe of 50 S ribosomal subunit structure. Journal of molecular biology 13 9878356
1988 Potassium currents in rat cerebellar Purkinje neurones maintained in culture in L15 (Leibovitz) medium. Neuroscience letters 12 2456497
2020 Up-Regulated CCDC34 Contributes to the Proliferation and Metastasis of Hepatocellular Carcinoma. OncoTargets and therapy 10 32021254
2023 MNX1 facilitates the malignant progress of lung adenocarcinoma through transcriptionally upregulating CCDC34. Oncology letters 9 37415626
2019 Enterococcus faecium L-15 Cell-Free Extract Improves the Chondrogenic Differentiation of Human Dental Pulp Stem Cells. International journal of molecular sciences 9 30709061
2006 Identification and purification of a novel adhesion-associated protein in a new strain of Lactobacillus, L15, from flounder (Paralichthys olivaceus). Veterinary microbiology 9 17350186
2021 RABL2A-CCDC34 Axis Promotes Sorafenib Resistance in Hepatocellular Carcinoma. DNA and cell biology 7 34767735
1999 Characterization of cDNAs encoding cytoplasmic ribosomal protein L15 and L27a in petunia (Petunia hybrida): primary structures and coordinate expression. Gene 7 9931480
2024 A novel missense mutation of CCDC34 causes male infertility with oligoasthenoteratozoospermia in a consanguineous Pakistani family. Asian journal of andrology 6 38856307
2022 Detection of mRNAs of Ribosomal Protein L15 and E-Cadherin in Living Circulating Tumor Cells at Single Cell Resolution To Study Tumor Heterogeneity. Analytical chemistry 6 35856393
2020 Enterococcus faecium L-15 Extract Enhances the Self-Renewal and Proliferation of Mouse Skin-Derived Precursor Cells. Probiotics and antimicrobial proteins 6 32162154
1999 Cloning and characterization of the L15 ribosomal protein gene homologue from the crayfish Orconectes limosus. Biochemical and biophysical research communications 6 10080916
1994 The primary structure of rat ribosomal protein L15. Biochemical and biophysical research communications 6 8198562
1991 Chloroplast ribosomal protein L15, like L1, L13 and L21, is significantly larger than its E. coli homologue. FEBS letters 6 2037044
2024 CCDC34 maintains stemness phenotype through β-catenin-mediated autophagy and promotes EGFR-TKI resistance in lung adenocarcinoma. Cancer gene therapy 5 39587349
2023 Interaction of Camptothecin Anticancer Drugs with Ribosomal Proteins L15 and L11: A Molecular Docking Study. Molecules (Basel, Switzerland) 5 36838813
2016 Bacterial type B RNase P: functional characterization of the L5.1-L15.1 tertiary contact and antisense inhibition. RNA (New York, N.Y.) 5 27604960
1980 Cellular quiescence modulates and replication of L15 mutants of vesicular stomatitis virus. The Journal of general virology 3 6161988
2019 L1-ORF1p and Ago2 are involved in a siRNA-mediated regulation for promoter activity of L1-5'UTR. Folia histochemica et cytobiologica 2 31112282
1995 The Thermoplasma acidophilum rpl15 gene encodes a homologue of eukaryotic ribosomal proteins L15/YL10. Biochemical and biophysical research communications 2 7733938
2006 [The study of ribosomal protein l15 cDNA sequences as a molecular marker in the teleostei phylogenetic analysis]. Yi chuan = Hereditas 1 16520312
2002 In vitro safety profile of G-CSF-mobilized whole blood after storage for 7 days in an infusable-grade L15 medium. Transfusion 1 12076290
1984 Characterization of an amber mutation in the structural gene for ribosomal protein L15, which impairs the expression of the protein export gene, secY, in Escherichia coli. The EMBO journal 1 16453596
2025 Circular RNA ribosomal protein L15 accelerates epithelial mesenchymal transformation and tumour growth in non-small cell lung carcinoma via modulating the microRNA-518c-3p/WD repeat protein 1 axis. Archives of physiology and biochemistry 0 41201114