Affinage

CCND1

G1/S-specific cyclin-D1 · UniProt P24385

Length
295 aa
Mass
33.7 kDa
Annotated
2026-06-09
100 papers in source corpus 30 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/6 claims corpus-supported (67%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCND1 (cyclin D1/PRAD1) is a G1 cyclin that drives the G1→S phase transition by forming an active kinase complex: it was first shown to associate with and activate cdc2-family kinases, conferring histone H1 kinase activity (PMID:1826542), and its mRNA peaks in G1 and falls before S phase in synchronized cells (PMID:1383201). In partnership with CDK6, CCND1 phosphorylates and inactivates pRb to de-repress E2F target genes; this activity requires an intact kinase and, in chondrocytes, drives pRb hyperphosphorylation, E2F target dysregulation and p53-dependent apoptosis (PMID:23624920), while CCND1 has no cell-cycle activity independent of CDK6, and p27 arrests cells by blocking CDK6/CCND1 complex assembly (PMID:30317923). Beyond its canonical kinase role, CCND1 acts in the nucleus to remodel chromatin, sequestering HDAC1/HDAC2 away from the SOX11 locus to increase H3K9/K14 acetylation and SOX11 transcription in mantle cell lymphoma (PMID:30530749). CCND1 expression is controlled at every level. Transcription is activated through promoter elements bound by OCT4 (PMID:25128069), phospho-CREB downstream of VRK1 (PMID:18713830), a SETDB1–ERG complex (PMID:33044755), AURKB-deposited H3S10ph marks (PMID:31982864), MAZ phase-separated condensates nucleated on promoter G-quadruplexes that compartmentalize BRD4/MED1/CDK9/Pol II (PMID:38316778), and β-catenin signaling driven by JAM3–LRP5→AKT→GSK3β (PMID:29584620), and is repressed by parafibromin (PMID:15580289) and by JARID2-mediated H3K27me3 (PMID:25939703). mRNA fate is set by 3' UTR AU-rich elements and alternative polyadenylation (PMID:8204893, PMID:29717174), by m6A marks read by YTHDF3/written by METTL3 in the 5' UTR to promote translation (PMID:35112553) and erased by FTO to prevent YTHDF2-dependent decay (PMID:33651996), and by RNA-binding translational activators La (PMID:20856207) and MYF5 (PMID:26819411). Protein abundance is governed by Thr286 phosphorylation-dependent ubiquitin–proteasome degradation, which is opposed by the USP10 deubiquitinase that removes K48-linked chains (PMID:33184448). CCND1 is the BCL-1 oncogene, identified through the t(11;14)/variant Ig translocations, and functions as an oncogene by overexpression of the wild-type protein rather than coding mutation (PMID:8426754, PMID:7621424, PMID:8049438, PMID:1394169, PMID:8426477); overexpression arises from translocation, 3' UTR stabilization, or trans-acting regulation (PMID:8204893, PMID:9591636), and cancer-associated point mutations (E36K, Y44D, C47S) that block Thr286 phosphorylation further stabilize nuclear CCND1 and confer ibrutinib resistance (PMID:27713153).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1991 High

    Established that the PRAD1 gene product is a functional cyclin, answering whether this oncogene candidate had cyclin-kinase activity.

    Evidence p13suc1 bead pulldown and histone H1 kinase reconstitution in clam embryo lysates

    PMID:1826542

    Open questions at the time
    • Used cdc2 rather than the physiological CDK4/6 partner
    • Did not establish the cell-cycle phase of action in mammalian cells
  2. 1992 Medium

    Linked CCND1 to G1 control by showing its expression is cell-cycle regulated, establishing when in the cycle it acts.

    Evidence Northern blot of synchronized HeLa and mammary epithelial cells

    PMID:1383201

    Open questions at the time
    • Correlative expression timing, not a functional perturbation
    • Did not identify the downstream substrate
  3. 1993 High

    Defined the promoter architecture and showed CCND1 is oncogenic through wild-type overexpression, not coding mutation, settling the mechanism of its oncogene activity.

    Evidence Genomic cloning/promoter characterization and direct cDNA sequencing of overexpressed tumor transcripts

    PMID:7621424 PMID:7687458 PMID:8426754

    Open questions at the time
    • Did not identify the trans-acting factors driving overexpression
    • E2F motif function inferential at this stage
  4. 1994 High

    Identified CCND1 as the BCL-1 oncogene and revealed 3' UTR rearrangement as a posttranscriptional overexpression mechanism, explaining how translocation deregulates the gene.

    Evidence Variant Ig translocation breakpoint mapping and actinomycin D mRNA half-life measurements in t(11;14) cell lines

    PMID:1394169 PMID:8049438 PMID:8204893 PMID:8426477

    Open questions at the time
    • Did not identify the trans-factors binding the AU-rich elements
    • Half-life measured in cell lines, not primary tumors
  5. 1996 Medium

    Placed CCND1 functionally upstream of pRb and demonstrated oncogenic collaboration, situating it within the cell-cycle and transformation network.

    Evidence MCL clinical specimen analysis (IHC/Western/Northern/flow) and rat fibroblast focus formation with ras and mutant p53

    PMID:8623927 PMID:8641982

    Open questions at the time
    • pRb relationship inferred from correlation in patient samples
    • Focus formation does not define the molecular mechanism of collaboration
  6. 1998 Medium

    Showed that overexpression in copy-number-normal tumors is biallelic, establishing trans-acting regulation as a mechanism distinct from cis mutation.

    Evidence Allele-specific RT-PCR-RFLP at the NciI polymorphism in heterozygous tumor lines

    PMID:9591636

    Open questions at the time
    • Did not identify the responsible trans-acting regulator
  7. 2010 High

    Identified translational control of CCND1, showing RNA-binding proteins drive its synthesis beyond transcription.

    Evidence RIP, IRES-reporter assay, and rescue in CCND1-null cells for La

    PMID:20856207

    Open questions at the time
    • IRES mechanism vs cap-dependent contribution not quantified
    • Tissue contexts of La-dependent control undefined
  8. 2013 High

    Demonstrated that CCND1/CDK6 kinase activity is mechanistically required for pRb phosphorylation and downstream consequences in vivo.

    Evidence Chondrocyte-specific transgenic overexpression with kinase-dead mutants and p53-KO rescue

    PMID:23624920

    Open questions at the time
    • Chondrocyte-specific; generalization to other lineages assumed
    • Did not address CDK4 partnership
  9. 2016 High

    Defined how cancer-associated point mutations stabilize CCND1 and confer drug resistance, linking Thr286-dependent degradation to therapy response.

    Evidence Site-directed mutagenesis with Thr286 phospho-Western, immunofluorescence, and ibrutinib viability assay; MYF5 RNA-binding/translation assays

    PMID:26819411 PMID:27713153

    Open questions at the time
    • Did not identify the relevant E3 ligase
    • Ibrutinib resistance mechanism downstream of CCND1 not detailed
  10. 2018 High

    Revealed non-canonical and multilayered control: CCND1 sequesters HDACs to remodel chromatin, requires CDK6 for cell-cycle function, and is regulated by APA, SETDB1-ERG, OCT4, and JAM3-driven β-catenin signaling.

    Evidence Co-IP, ChIP for histone marks, CRISPR PAS editing, luciferase promoter mutagenesis, and genetic KO with serial transplantation across multiple systems

    PMID:25128069 PMID:25939703 PMID:29584620 PMID:29717174 PMID:30317923 PMID:30530749 PMID:33044755

    Open questions at the time
    • HDAC sequestration generality across loci unknown
    • Many transcriptional inputs validated in single cancer contexts
  11. 2020 High

    Established deubiquitination and chromatin/epigenetic transcriptional inputs as additional control points stabilizing CCND1 protein and activating its transcription.

    Evidence USP10 K48-ubiquitination and Co-IP assays; AURKB H3S10ph ChIP at CCND1 promoter with inhibitor and xenograft

    PMID:31982864 PMID:33184448

    Open questions at the time
    • USP10 regulation upstream undefined
    • AURKB study at Medium confidence with limited orthogonal validation
  12. 2022 High

    Detailed m6A-dependent translational and stability control and G-quadruplex/condensate-driven transcription, defining the most recent layers of CCND1 regulation.

    Evidence Ythdf3-KO mouse with Ccnd1-rescue and m6A mapping; FTO m6A-RIP/stability assays; MAZ G4-binding and phase-separation mutagenesis with xenograft

    PMID:33651996 PMID:35112553 PMID:38316778

    Open questions at the time
    • Interplay between m6A writers/erasers/readers at CCND1 not integrated
    • Condensate mechanism studied in HCC only

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many transcriptional, RNA-stability, translational, and protein-stability inputs are integrated to set CCND1 levels in a given cell type, and which are tractable therapeutic nodes, remains unresolved.
  • No unified quantitative model of competing regulatory inputs
  • Physiological E3 ligase for Thr286-dependent degradation not identified in this corpus
  • Endogenous CDK4 partnership not addressed in the timeline

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 3
Partners
CDK6CDKN1BHDAC1HDAC2USP10
Complex memberships
CDK6/cyclin D1

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 PRAD1/cyclin D1 protein can be isolated with p13suc1 beads (which bind cdc2 and related kinases), and addition of PRAD1 protein to interphase clam embryo lysates containing inactive p34cdc2 kinase induces phosphorylation of histone H1, a preferred cdc2 substrate, demonstrating that PRAD1 encodes a cyclin capable of forming a complex with and activating p34cdc2 kinase. p13suc1 bead pulldown from interphase clam embryo lysates; histone H1 kinase assay Nature High 1826542
1992 PRAD1/cyclin D1 mRNA levels vary dramatically across the cell cycle in HeLa cells, peaking in G1 and declining before S phase, consistent with a role in regulating G1-S phase progression; in normal mammary epithelial cells synchronized by growth factor deprivation, PRAD1 expression peaked in G1. Northern blot analysis of synchronized HeLa and primary mammary epithelial cells The Journal of biological chemistry Medium 1383201
1993 The PRAD1/cyclin D1 gene spans ~15 kb, has 5 exons, and its promoter contains Sp1 binding sites, no TATA box, and an E2F binding motif near the major transcription start site, the latter potentially involved in cell cycle-dependent expression. Genomic cloning, sequencing, promoter characterization Genes, chromosomes & cancer Medium 7687458
1993 Sequencing of the overexpressed PRAD1 transcript from a parathyroid adenoma and a centrocytic lymphoma with clonal PRAD1 rearrangements showed coding sequences identical to the normal PRAD1 cDNA, indicating that PRAD1 functions as an oncogene through overexpression of its normal (wild-type) protein, not through coding-sequence mutation. Direct cDNA sequencing of overexpressed transcripts from primary tumors Oncogene High 7621424 8426754
1994 The t(11;22)(q13;q11) variant translocation places the Ig lambda light chain gene 3' of the PRAD1 gene, resulting in PRAD1 mRNA overexpression; since only PRAD1 lies between the Ig heavy chain and light chain breakpoints, this identifies PRAD1/cyclin D1 as the BCL-1 oncogene. Molecular analysis of variant translocation breakpoints by Southern blot and Northern blot Blood High 1394169 8049438 8426477
1994 Rearrangements within the 3' UTR of CCND1 eliminate AU-rich mRNA destabilizing sequences; CCND1 mRNA half-life in t(11;14)-bearing cell lines is >3 hours versus ~0.5 hours in normal tissues, indicating that posttranscriptional stabilization through 3' UTR rearrangement is a mechanism of CCND1 overexpression. Southern blot mapping of 3' UTR rearrangements; mRNA half-life measurement by Northern blot after actinomycin D treatment Blood High 8204893
1996 Cyclin D1 (CCND1) overexpression in mantle cell lymphoma (MCL) cells promotes cell proliferation by overcoming pRb growth suppression; pRb is expressed and phosphorylated in MCL in proportion to proliferative activity, and cyclin D1 mRNA levels are independent of pRb expression level, consistent with cyclin D1 acting upstream of pRb inactivation. Immunohistochemistry, Western blot, Northern blot, flow cytometry in MCL patient samples The American journal of pathology Medium 8623927
1996 Cyclin D1 (CCND1) collaborates with mutated p53 and activated ras in oncogenic transformation: cyclin D1 alone or with ras or p53-mt was insufficient for focus formation of rat embryonic fibroblasts, but enhanced focus formation and reduced serum dependency when co-transfected with ras and p53-mt transformants, and accelerated in vivo growth in nude mice. Focus formation assay in rat embryonic fibroblasts; nude mouse xenograft assay Japanese journal of cancer research Medium 8641982
1998 In breast, sarcoma, and colon cancer cell lines with cyclin D1 overexpression but normal gene copy number, elevated CCND1 mRNA is derived equally from both alleles (by RT-PCR-RFLP at NciI polymorphism), indicating that overexpression results from a trans-acting regulatory influence rather than a clonal cis-acting somatic mutation. RT-PCR with RFLP (NciI digest) to assess allele-specific mRNA expression in heterozygous tumor cell lines Genes, chromosomes & cancer Medium 9591636
2005 Parafibromin (HRPT2 product) inhibits cell proliferation and blocks cyclin D1 (CCND1) expression; a cancer-associated Leu64Pro missense mutant of parafibromin fails to suppress CCND1 expression or inhibit proliferation, placing parafibromin as a negative regulator of CCND1. Transient overexpression of wild-type vs. mutant parafibromin in cells; cell proliferation assay; Western blot for CCND1 Oncogene Medium 15580289
2008 VRK1 phosphorylates CREB at Ser133 in vitro and facilitates recruitment of phospho-CREB to the CRE element in the CCND1 promoter, thereby activating CCND1 transcription; a kinase-dead VRK1 mutant or VRK1 siRNA knockdown fails to activate CREB and CCND1 expression, and VRK1 mediates Myc-stimulated CCND1 induction. In vitro kinase assay (VRK1 phosphorylation of CREB); chromatin immunoprecipitation (ChIP); siRNA knockdown; kinase-dead mutant overexpression; luciferase reporter for CRE Journal of cell science High 18713830
2010 The RNA-binding protein La associates with CCND1 mRNA and promotes CCND1 IRES-dependent translation; La depletion reduces CCND1 protein and cell proliferation, which is rescued by re-expression of La but not in CCND1 knockout cells, establishing a functional La→CCND1 translation axis. siRNA knockdown; in vivo RNP immunoprecipitation (RIP); CCND1 IRES-reporter assay; rescue in CCND1 knockout cells Oncogene High 20856207
2013 Overexpression of Cdk6/Ccnd1 together (but not either alone) in chondrocytes highly phosphorylates pRb, upregulates p107, inhibits chondrocyte maturation, and causes p53-dependent apoptosis; kinase-negative Cdk6/cyclin D1 abolishes all these effects, demonstrating that Cdk6/Ccnd1 kinase activity is required for pRb phosphorylation, E2f target gene dysregulation, and apoptosis in chondrocytes. Transgenic mouse overexpression (chondrocyte-specific Col2a1-Cdk6 and/or Ccnd1); kinase-dead mutant; BrdU/TUNEL labeling; Western blot for pRb phosphorylation; p53 knockout rescue Oncogene High 23624920
2016 CCND1 mutations E36K, Y44D, and C47S increase CCND1 protein stability by attenuating phosphorylation at Thr286 (required for ubiquitin-proteasome-mediated proteolysis), and the mutant proteins preferentially localize to the nucleus; forced expression of wild-type or mutant CCND1 increases MCL cell resistance to ibrutinib. Site-directed mutagenesis; Western blot for Thr286 phosphorylation and protein levels; immunofluorescence for subcellular localization; cell viability assay with ibrutinib Oncotarget High 27713153
2016 MYF5 binds the 3' UTR and coding region of Ccnd1 mRNA (by RIP, biotin-RNA pulldown, UV-crosslinking, gel shift) and promotes CCND1 translation; MYF5 silencing reduces CCND1 protein and myoblast proliferation, which is partially rescued by restoring CCND1 abundance. RNP immunoprecipitation (RIP), biotin-RNA pulldown, UV-crosslinking, gel shift, siRNA knockdown, polysome/translation assay Nucleic acids research High 26819411
2018 CCND1 interacts with and sequesters HDAC1 and HDAC2 from the SOX11 locus, leading to increased acetylation of histones H3K9 and H3K14 at SOX11 and upregulation of SOX11 transcription in MCL. Co-immunoprecipitation; ChIP for H3K9/14Ac at SOX11 locus; siRNA knockdown of HDAC1/2; HDAC inhibitor (vorinostat) treatment; ectopic CCND1 expression Blood High 30530749
2018 p27 inhibits the formation of the CDK6/CCND1 complex (demonstrated by co-immunoprecipitation and immunofluorescence), causing G1/S cell cycle arrest and inhibiting proliferation; p27 does not directly alter CDK6 or CCND1 expression levels, and CCND1 does not regulate the cell cycle independently of CDK6. Co-immunoprecipitation; immunofluorescence; flow cytometry (cell cycle); MTT proliferation assay; Western blot Cell cycle Medium 30317923
2018 Cell cycle regulation by alternative polyadenylation (APA) of CCND1: CRISPR/Cas9 editing of the weak proximal poly(A) signal to a canonical PAS forces use of the proximal APA site, producing shorter CCND1 3' UTR transcripts that accelerate the cell cycle and promote cell proliferation. CRISPR/Cas9 PAS editing; cell cycle profiling by flow cytometry; cell proliferation assay Scientific reports Medium 29717174
2020 USP10 deubiquitinase interacts with CCND1 and prevents its K48-linked polyubiquitination, thereby stabilizing CCND1 protein; USP10 knockdown downregulates CCND1 and causes GBM cell cycle arrest at G1 and apoptosis; the natural compound acevaltrate suppresses USP10-mediated CCND1 deubiquitination. Co-immunoprecipitation; ubiquitination assay (K48 vs K63 linkage); sgRNA-mediated USP10 knockdown; flow cytometry (cell cycle and apoptosis); Western blot Acta pharmacologica Sinica High 33184448
2020 AURKB activates CCND1 transcription through phosphorylation of histone H3 at Ser10 (H3S10ph) at the CCND1 promoter; AURKB silencing reduces H3S10ph at the CCND1 promoter and decreases CCND1 expression, arresting cells at G2/M; the AURKB inhibitor AZD1152 also suppresses CCND1 expression. siRNA knockdown; ChIP for H3S10ph at CCND1 promoter; flow cytometry; Western blot; AZD1152 inhibitor treatment; in vivo xenograft Aging Medium 31982864
2022 YTHDF3 m6A reader and METTL3 m6A writer regulate translation of Ccnd1 mRNA through m6A modification on the 5' UTR of Ccnd1; dysfunction of Ythdf3 or Mettl3 causes translational defects in Ccnd1 and impairs HSC reconstitution capacity; enforced Ccnd1 expression fully rescues Ythdf3-/- HSC defects. Ythdf3 knockout mouse; m6A sequencing/mapping; polysome/translation assay; genetic rescue with enforced Ccnd1 expression; bone marrow reconstitution assay Haematologica High 35112553
2021 FTO m6A demethylase controls CCND1 mRNA stability through YTHDF2-mediated degradation: FTO knockdown increases m6A on CCND1 mRNA, leading to YTHDF2-dependent mRNA degradation, decreased CCND1 expression, G1 phase delay, and impaired myoblast proliferation. siRNA knockdown of FTO; m6A RNA immunoprecipitation; RNA stability assay; flow cytometry (cell cycle); Western blot for CCND1 Experimental cell research Medium 33651996
2024 G-quadruplexes (G4s) in the CCND1 promoter recruit MAZ transcription factor through its zinc finger 2 domain, facilitating MAZ phase-separated condensate formation (requiring ZF3-5) that compartmentalizes coactivators BRD4, MED1, CDK9, and active RNA Pol II to activate CCND1 transcription; MAZ mutants lacking G4 binding or phase separation cannot form nuclear puncta and fail to promote hepatocellular carcinoma cell proliferation. G4-specific binding assay; domain mutagenesis; co-localization/co-immunoprecipitation of MAZ condensates with coactivators; xenograft tumor assay; ChIP for active Pol II and histone marks at CCND1 promoter Nature communications High 38316778
2015 JARID2 negatively regulates CCND1 expression by increasing H3K27 trimethylation at the CCND1 promoter (ChIP assay); JARID2 knockdown promotes leukemia cell G1/S transition and proliferation, while ectopic JARID2 expression inhibits these effects. ChIP for H3K27me3 at CCND1 promoter; siRNA knockdown and ectopic overexpression; flow cytometry (cell cycle); Western blot International journal of hematology Medium 25939703
2018 SETDB1 histone methyltransferase interacts with transcription factor ERG to promote CCND1 transcription by binding to the CCND1 promoter region; SETDB1 overexpression increases CCND1 expression and gastric cancer cell proliferation, while SETDB1 suppression has the opposite effect. Co-immunoprecipitation (SETDB1-ERG interaction); ChIP at CCND1 promoter; siRNA knockdown and overexpression; cell proliferation and in vivo assays The Journal of pathology Medium 33044755
2014 OCT4 directly binds the octamer motif (ATTTTGCAT) in the CCND1 promoter to activate CCND1 transcription; mutation of the octamer motif abolishes OCT4-induced CCND1 promoter activity, while CCND1 suppression does not affect OCT4 expression, establishing a unidirectional OCT4→CCND1 transcriptional regulatory axis. Luciferase reporter assay with wild-type and octamer-mutant CCND1 promoters; siRNA knockdown; Western blot; cell cycle analysis; xenograft Cancer letters Medium 25128069
2018 JAM3 directly associates with LRP5 to activate the PDK1/AKT pathway, resulting in GSK3β downregulation and activation of β-catenin/CCND1 signaling, maintaining leukemia-initiating cell self-renewal; Jam3 deletion abrogates leukemogenesis without affecting normal hematopoietic stem cells. Co-immunoprecipitation (JAM3-LRP5); JAM3 genetic deletion (MLL-AF9 murine AML model); serial transplantation; pathway inhibitor studies; Western blot The Journal of clinical investigation High 29584620

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature 1293 1826542
1991 PRAD1, a candidate BCL1 oncogene: mapping and expression in centrocytic lymphoma. Proceedings of the National Academy of Sciences of the United States of America 467 1682919
1992 Identification and cloning of two overexpressed genes, U21B31/PRAD1 and EMS1, within the amplified chromosome 11q13 region in human carcinomas. Oncogene 362 1532244
1992 Gene rearrangement and overexpression of PRAD1 in lymphoid malignancy with t(11;14)(q13;q32) translocation. Oncogene 235 1535701
1991 Rearrangement and overexpression of D11S287E, a candidate oncogene on chromosome 11q13 in benign parathyroid tumors. Oncogene 235 2011400
1992 Cloning and characterization of human cyclin D3, a cDNA closely related in sequence to the PRAD1/cyclin D1 proto-oncogene. The Journal of biological chemistry 153 1383201
1996 Cyclin D1/PRAD1 expression in parathyroid adenomas: an immunohistochemical study. The Journal of clinical endocrinology and metabolism 148 8626826
1993 PRAD1/cyclin D1 proto-oncogene: genomic organization, 5' DNA sequence, and sequence of a tumor-specific rearrangement breakpoint. Genes, chromosomes & cancer 146 7687458
1999 Amplification and expression of cyclin D genes (CCND1, CCND2 and CCND3) in human malignant gliomas. Brain pathology (Zurich, Switzerland) 142 10416984
1998 Mechanism of cyclin D1 (CCND1, PRAD1) overexpression in human cancer cells: analysis of allele-specific expression. Genes, chromosomes & cancer 128 9591636
1994 Rearrangement of CCND1 (BCL1/PRAD1) 3' untranslated region in mantle-cell lymphomas and t(11q13)-associated leukemias. Blood 128 8204893
1992 Characterization of chromosome 11 translocation breakpoints at the bcl-1 and PRAD1 loci in centrocytic lymphoma. Cancer research 125 1394169
1993 Chromosome 11 translocation breakpoints at the PRAD1/cyclin D1 gene locus in centrocytic lymphoma. Leukemia 124 8426477
2007 Amplification of CCND1 and PAK1 as predictors of recurrence and tamoxifen resistance in postmenopausal breast cancer. Oncogene 122 17486065
2005 Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2, regulates cyclin D1/PRAD1 expression. Oncogene 122 15580289
1999 Expression of PRAD1/cyclin D1, retinoblastoma gene products, and Ki67 in parathyroid hyperplasia caused by chronic renal failure versus primary adenoma. Kidney international 100 10201002
2018 LncRNA HOTAIR Regulates CCND1 and CCND2 Expression by Sponging miR-206 in Ovarian Cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 97 30205383
1995 Expression of cyclin D1 protein in centrocytic/mantle cell lymphomas with and without rearrangement of the BCL1/cyclin D1 gene. Human pathology 94 7545645
1997 Detection of cyclin D1 (bcl-1, PRAD1) overexpression by a simple competitive reverse transcription-polymerase chain reaction assay in t(11;14)(q13;q32)-bearing B-cell malignancies and/or mantle cell lymphoma. Blood 89 9028328
1995 Oesophageal cancer and amplification of the human cyclin D gene CCND1/PRAD1. British journal of cancer 88 7819051
2008 VRK1 phosphorylates CREB and mediates CCND1 expression. Journal of cell science 84 18713830
1994 A variant chromosome translocation at 11q13 identifying PRAD1/cyclin D1 as the BCL-1 gene. Blood 84 8049438
1995 Increased expression of the PRAD-1/CCND1 gene in hairy cell leukaemia. British journal of haematology 78 8547115
2013 OCT4 increases BIRC5 and CCND1 expression and promotes cancer progression in hepatocellular carcinoma. BMC cancer 72 23433354
1996 Involvement of the CCND1 gene in hairy cell leukemia. Annals of oncology : official journal of the European Society for Medical Oncology 69 8740788
1996 Expression of retinoblastoma gene product (pRb) in mantle cell lymphomas. Correlation with cyclin D1 (PRAD1/CCND1) mRNA levels and proliferative activity. The American journal of pathology 68 8623927
2006 Polymorphisms in XRCC1, XRCC3, and CCND1 and survival after treatment for metastatic breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 67 17116943
2020 AURKB promotes gastric cancer progression via activation of CCND1 expression. Aging 65 31982864
2016 CCND1 mutations increase protein stability and promote ibrutinib resistance in mantle cell lymphoma. Oncotarget 65 27713153
2010 The RNA-binding protein La contributes to cell proliferation and CCND1 expression. Oncogene 65 20856207
2003 Rearrangements and increased expression of cyclin D1 (CCND1) in neuroblastoma. Genes, chromosomes & cancer 65 12557224
1993 Coding sequence of the overexpressed transcript of the putative oncogene PRAD1/cyclin D1 in two primary human tumors. Oncogene 64 8426754
2018 Cell Cycle Regulation by Alternative Polyadenylation of CCND1. Scientific reports 60 29717174
2020 Suppression of the USP10/CCND1 axis induces glioblastoma cell apoptosis. Acta pharmacologica Sinica 58 33184448
2019 LINC01355 suppresses breast cancer growth through FOXO3-mediated transcriptional repression of CCND1. Cell death & disease 57 31243265
2018 JAM3 maintains leukemia-initiating cell self-renewal through LRP5/AKT/β-catenin/CCND1 signaling. The Journal of clinical investigation 57 29584620
1994 Monoclonal antibody against PRAD1/cyclin D1 stains nuclei of tumor cells with translocation or amplification at BCL-1 locus. Japanese journal of cancer research : Gann 57 7961120
2016 Novel RNA-binding activity of MYF5 enhances Ccnd1/Cyclin D1 mRNA translation during myogenesis. Nucleic acids research 56 26819411
2020 ITGA2 promotes expression of ACLY and CCND1 in enhancing breast cancer stemness and metastasis. Genes & diseases 52 34179312
1995 Abnormalities in the PRAD1 (CYCLIN D1/BCL-1) oncogene are frequent in cervical and vulvar squamous cell carcinoma cell lines. Cancer 52 7812927
2018 LINC00152 promotes cell cycle progression in hepatocellular carcinoma via miR-193a/b-3p/CCND1 axis. Cell cycle (Georgetown, Tex.) 51 29895195
2020 MiR-93 suppresses tumorigenesis and enhances chemosensitivity of breast cancer via dual targeting E2F1 and CCND1. Cell death & disease 47 32796817
1997 Tumor dormancy and cell signaling. V. Regrowth of the BCL1 tumor after dormancy is established. Blood 47 9192767
2023 CircNFATC3 promotes the proliferation of gastric cancer through binding to IGF2BP3 and restricting its ubiquitination to enhance CCND1 mRNA stability. Journal of translational medicine 46 37340423
2009 Chronological expression of Wnt target genes Ccnd1, Myc, Cdkn1a, Tfrc, Plf1 and Ramp3. Cell biology international 46 19353769
2002 MYEOV: a candidate gene for DNA amplification events occurring centromeric to CCND1 in breast cancer. International journal of cancer 46 12448002
1995 Absence of cyclin D1/PRAD1 point mutations in human breast cancers and parathyroid adenomas and identification of a new cyclin D1 gene polymorphism. Cancer letters 46 7621424
2006 Alterations of the CCND1 and HER-2/neu (ERBB2) proteins in esophageal and gastric cancers. Cancer genetics and cytogenetics 45 16490596
2012 Cyclin D1 (CCND1) expression is involved in estrogen receptor beta (ERβ) in human prostate cancer. The Prostate 44 23060014
2024 G-quadruplexes promote the motility in MAZ phase-separated condensates to activate CCND1 expression and contribute to hepatocarcinogenesis. Nature communications 43 38316778
2019 LncRNA HCG18 contributes to nasopharyngeal carcinoma development by modulating miR-140/CCND1 and Hedgehog signaling pathway. European review for medical and pharmacological sciences 43 31841193
1997 Abnormal expression of CCND1 and RB1 in resection margin epithelia of lung cancer patients. British journal of cancer 42 9192978
2016 A study of CCND1 with epithelial ovarian cancer cell proliferation and apoptosis. European review for medical and pharmacological sciences 39 27831653
2005 External imaging of CCND1, MYC, and KRAS oncogene mRNAs with tumor-targeted radionuclide-PNA-peptide chimeras. Annals of the New York Academy of Sciences 39 16382049
2020 FGFR1 regulates proliferation and metastasis by targeting CCND1 in FGFR1 amplified lung cancer. Cell adhesion & migration 37 32380883
2011 CCND1 amplification and protein overexpression in oral squamous cell carcinoma of young patients. Head & neck 37 21254295
2018 p27 inhibits CDK6/CCND1 complex formation resulting in cell cycle arrest and inhibition of cell proliferation. Cell cycle (Georgetown, Tex.) 36 30317923
2019 CCND1 silencing suppresses liver cancer stem cell differentiation through inhibiting autophagy. Human cell 35 31667787
2018 The long noncoding RNA SNHG1 promotes nucleus pulposus cell proliferation through regulating miR-326 and CCND1. American journal of physiology. Cell physiology 35 29466672
1995 The positive nuclear staining observed with monoclonal antibody against PRAD1/cyclin D1 correlates with mRNA expression in mantle cell lymphoma. Japanese journal of cancer research : Gann 35 7591969
2024 Morusin Alleviates Aortic Valve Calcification by Inhibiting Valve Interstitial Cell Senescence Through Ccnd1/Trim25/Nrf2 Axis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 33 38502885
2020 SETDB1 promotes gastric carcinogenesis and metastasis via upregulation of CCND1 and MMP9 expression. The Journal of pathology 33 33044755
2008 Combined effect of CCND1 and COMT polymorphisms and increased breast cancer risk. BMC cancer 32 18194538
2018 Regulation of SOX11 expression through CCND1 and STAT3 in mantle cell lymphoma. Blood 31 30530749
2012 Promoter-associated noncoding RNA from the CCND1 promoter. Methods in molecular biology (Clifton, N.J.) 31 22113303
2018 CHAF1A interacts with TCF4 to promote gastric carcinogenesis via upregulation of c-MYC and CCND1 expression. EBioMedicine 30 30449701
2014 Transcription factor OCT4 promotes cell cycle progression by regulating CCND1 expression in esophageal carcinoma. Cancer letters 30 25128069
2005 Cyclin D1 gene (CCND1) polymorphism and the risk of squamous cell carcinoma of the larynx. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 30 16258756
2022 YTHDF3 modulates hematopoietic stem cells by recognizing RNA m6A modification on Ccnd1. Haematologica 29 35112553
2017 HNRNPK inhibits gastric cancer cell proliferation through p53/p21/CCND1 pathway. Oncotarget 29 29262567
2018 The deregulation of miR-17/CCND1 axis during neuroendocrine transdifferentiation of LNCaP prostate cancer cells. PloS one 28 30001402
2015 JARID2 inhibits leukemia cell proliferation by regulating CCND1 expression. International journal of hematology 28 25939703
2019 Baicalein blocked cervical carcinoma cell proliferation by targeting CCND1 via Wnt/β-catenin signaling pathway. Artificial cells, nanomedicine, and biotechnology 27 31284780
2022 Circular RNA RHOT1 Regulates miR-142-5p/CCND1 to Participate in Chondrocyte Autophagy and Proliferation in Osteoarthritis. Journal of immunology research 26 35300071
2017 The association between CCND1 G870A polymorphism and colorectal cancer risk: A meta-analysis. Medicine 26 29049220
2021 FTO regulates myoblast proliferation by controlling CCND1 expression in an m6A-YTHDF2-dependent manner. Experimental cell research 25 33651996
2013 Overexpression of Cdk6 and Ccnd1 in chondrocytes inhibited chondrocyte maturation and caused p53-dependent apoptosis without enhancing proliferation. Oncogene 25 23624920
2022 Identification of expression of CCND1-related lncRNAs in breast cancer. Pathology, research and practice 24 35803208
2021 PSMC2/CCND1 axis promotes development of ovarian cancer through regulating cell growth, apoptosis and migration. Cell death & disease 22 34294689
2022 EIF4A3-induced circCCNB1 (hsa_circ_0001495) promotes glioma progression by elevating CCND1 through interacting miR-516b-5p and HuR. Metabolic brain disease 19 35038081
2018 MicroRNA‑584 directly targets CCND1 and inhibits cell proliferation and invasion in pancreatic cancer. Molecular medicine reports 19 30431107
2010 CCND1 and CDKN1B polymorphisms and risk of breast cancer. Anticancer research 19 20683061
2021 hsa‑miR‑15a‑5p inhibits colon cell carcinoma via targeting CCND1. Molecular medicine reports 18 34414457
2020 LncRNA SNHG16 induces proliferation and fibrogenesis via modulating miR-141-3p and CCND1 in diabetic nephropathy. Gene therapy 18 32504027
1996 PRAD1/Cyclin D1 gene overexpression in mantle cell lymphoma. Leukemia & lymphoma 18 8907267
2022 CDC42EP3 promotes glioma progression via regulation of CCND1. Cell death & disease 17 35365622
1987 Receptor mediated leukemogenesis: murine leukemia virus interacts with BCL1 lymphoma cell surface IgM. The Journal of molecular and cellular immunology : JMCI 16 2855408
2021 MicroRNA-374b inhibits breast cancer progression through regulating CCND1 and TGFA genes. Carcinogenesis 15 33480984
2002 CCND1- and ERBB2-gene deregulation and PTEN mutation analyses in invasive lobular carcinoma of the breast. Molecular carcinogenesis 15 12203362
1996 Oncogenic collaboration of the cyclin D1 (PRAD1, bcl-1) gene with a mutated p53 and an activated ras oncogene in neoplastic transformation. Japanese journal of cancer research : Gann 15 8641982
2023 Protective role of circRNA CCND1 in ulcerative colitis via miR-142-5p/NCOA3 axis. BMC gastroenterology 14 36658474
2022 LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC. Frontiers in pharmacology 14 35814257
2019 Downregulation of TCEAL7 expression induces CCND1 expression in non-small cell lung cancer. Molecular biology reports 14 31321645
2008 Tissue array for Tp53, C-myc, CCND1 gene over-expression in different tumors. World journal of gastroenterology 14 19084934
1994 Fc gamma RII cross-linking inhibits anti-Ig-induced erg-1 and erg-2 expression in BCL1. Journal of immunology (Baltimore, Md. : 1950) 14 8133028
2021 CircRNA Circ-CCND1 Aggravates Hepatocellular Carcinoma Tumorigenesis by Regulating the miR-497-5p/HMGA2 Axis. Molecular biotechnology 13 34564768
2017 The EMSY Gene Collaborates with CCND1 in Non-Small Cell Lung Carcinogenesis. International journal of medical sciences 13 28824300
2008 Overcoming immunoescape mechanisms of BCL1 leukemia and induction of CD8+ T-cell-mediated BCL1-specific resistance in mice cured by targeted polymer-bound doxorubicin. Cancer research 13 19047168
1994 Clinical aspects of B-cell malignancy involving the BCL1/PRAD1 locus. International journal of hematology 13 8086622
1992 PRAD1 (cyclin D1): a parathyroid neoplasia gene on 11q13. Henry Ford Hospital medical journal 13 1483873

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