Affinage

LIN52

Protein lin-52 homolog · UniProt Q52LA3

Length
112 aa
Mass
12.5 kDa
Annotated
2026-06-10
34 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LIN52 is a small adaptor subunit of the evolutionarily conserved MuvB core that governs the assembly switch between transcriptional repression and activation of cell cycle genes (PMID:17531812, PMID:15545624). As part of the mammalian DREAM complex (p130/E2F4/DP plus the MuvB core proteins LIN9, LIN37, LIN52, LIN54, RBBP4), LIN52 helps repress more than 800 E2F target promoters during quiescence (PMID:17531812). DREAM assembly is gated by phosphorylation of LIN52 on serine 28 by DYRK1A: this modification is required for the complex to form and for cells to enter quiescence or undergo Ras-induced senescence (PMID:21498570), and DYRK1A activity toward LIN52 is itself enhanced by the Hippo kinase LATS2 (PMID:21498571). Mechanistically, phospho-S28 together with a suboptimal LxSxExL motif allows LIN52 to bind the LxCxE cleft of the p107/p130 pocket domains—but not Rb—with high affinity, thereby nucleating DREAM and explaining its pocket-protein specificity; CDK phosphorylation of p130 weakens this contact to disassemble DREAM upon cell cycle entry (PMID:25917549, PMID:33513914). Upon disassembly, LIN52 serves as the direct interface, alongside the LIN9 scaffold, that recruits B-Myb to form the activating MMB complex driving G2/M gene expression, and non-phosphorylated LIN52 favors this proliferative MMB/MMB-FoxM1 state over assembled DREAM (PMID:30224471, PMID:34728711). Within MuvB, LIN9 and LIN37 position LIN52 for transcription-factor engagement while the complex stabilizes the +1 nucleosome downstream of target TSSs to enforce repression (PMID:35082292). Loss of LIN52-dependent DREAM assembly has physiological consequences, including failure of chondrocyte cell-cycle arrest and defective endochondral bone formation in mice (PMID:24710275), and the LIN52 S28 axis is targeted by viral oncoproteins to override cell cycle control (PMID:28946006, PMID:33513914).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2003 Medium

    Established LIN52 as a conserved component of an Rb-pathway regulatory module before any biochemical mechanism was known, placing it genetically in cell-fate control.

    Evidence Genetic screen and epistasis identifying lin-52 as a class B synMuv gene in the lin-35 Rb pathway in C. elegans

    PMID:12750327

    Open questions at the time
    • No biochemical interaction or molecular function defined
    • Relationship to a defined protein complex unresolved
  2. 2004 High

    Demonstrated that the LIN52 ortholog is part of a physical Myb-MuvB repressor complex acting at developmental gene promoters, defining its biochemical context.

    Evidence Affinity co-purification of the Drosophila Myb-MuvB complex with ChIP and reporter assays

    PMID:15545624

    Open questions at the time
    • Specific role of LIN52 within the complex not isolated
    • Mammalian complex composition not yet established
  3. 2007 High

    Defined the mammalian DREAM complex containing LIN52 and showed it represses E2F target promoters in G0 and exchanges to a Myb-bound module in S phase, framing LIN52 within the repression-to-activation switch.

    Evidence Affinity-MS proteomics, ChIP-on-chip, siRNA knockdown and Co-IP in human cells; parallel C. elegans genetics linking lin-52 to programmed cell death

    PMID:17237514 PMID:17531812

    Open questions at the time
    • What signal triggers the DREAM-to-MMB switch unknown
    • Direct contacts of LIN52 within the complex unmapped
  4. 2011 High

    Identified the molecular trigger for DREAM assembly: DYRK1A phosphorylation of LIN52 S28, with LATS2 acting upstream, converting LIN52 into the regulatable node controlling quiescence and senescence.

    Evidence In vitro kinase assays, S28A mutagenesis, DYRK1A inhibition, Co-IP and cell cycle analysis; shRNA screen and kinase assay for the LATS2-DYRK1A link

    PMID:21498570 PMID:21498571

    Open questions at the time
    • Structural basis of how phospho-S28 enables binding not yet resolved
    • LATS2 link is indirect through DYRK1A (Medium confidence)
  5. 2014 High

    Showed in vivo that LIN52-dependent DREAM assembly is physiologically required for proliferative arrest, demonstrating organismal consequences of the phospho-switch.

    Evidence Gene-targeted DREAM-deficient mouse model with micro-CT/histology and DYRK inhibitor phenocopy in embryonic bone culture; Drosophila lin-52 null epistasis

    PMID:22688510 PMID:24710275

    Open questions at the time
    • Tissue-specific roles of LIN52 beyond chondrocytes not mapped
    • Mechanism connecting arrest failure to bone defect not detailed
  6. 2015 High

    Provided the structural mechanism for LIN52's pocket-protein specificity, showing phospho-S28 plus an LxSxExL motif binds the p107/p130 LxCxE cleft but not Rb, and that CDK phosphorylation of p130 drives disassembly.

    Evidence Crystal structure of LIN52-p107, in vitro binding, mutagenesis and reconstitution

    PMID:25917549

    Open questions at the time
    • Dynamics of CDK-driven disassembly in cells not quantified
    • How the same motif is repurposed for MMB assembly unresolved
  7. 2018 High

    Resolved how LIN52 builds the activating complex, showing it is the direct interface (with LIN9) recruiting B-Myb to form MMB, and that B-Myb reciprocally modulates DREAM and LIN52 levels via the S28 site.

    Evidence Crystal structure of the B-Myb-LIN52-LIN9 interface with binding assays; Co-IP and overexpression with domain and S28 mutants

    PMID:30206359 PMID:30224471

    Open questions at the time
    • Competition kinetics between DREAM and MMB assembly on LIN52 unquantified
    • B-Myb regulation of LIN52 levels mechanistically incomplete (Medium confidence)
  8. 2022 High

    Defined the architecture and chromatin engagement of MuvB, showing LIN9/LIN37 position LIN52 for transcription-factor binding while the complex stabilizes the +1 nucleosome to repress target genes.

    Evidence Crystal structure of a MuvB subcomplex, nucleosome reconstitution, and ChIP-seq in arrested cells; C. elegans LxCxE motif CRISPR mutagenesis with ChIP/RNA-seq

    PMID:35082292 PMID:35554539

    Open questions at the time
    • How nucleosome stabilization mechanistically silences transcription not detailed
    • Chromatin recruitment shown to depend on E2F-DP-Rb rather than Rb-MuvB in worm (Medium confidence)
  9. 2022 Medium

    Revealed a LIN52-specific requirement distinct from other MuvB subunits in stem cell fate, linking LIN52 to G2/M control and pluripotency maintenance.

    Evidence CRISPR knockout in mouse ESCs with cell cycle and pluripotency assays and Cyclin B1/Cdk1 rescue

    PMID:35148988

    Open questions at the time
    • Why LIN52 loss differs from LIN9/LIN37 loss mechanistically unexplained
    • Single lab, single cell type

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the LIN52 S28 phosphorylation state is dynamically set and reset to time the DREAM-to-MMB transition during the cell cycle, and how viral kinases/oncoproteins quantitatively override it, remains unresolved.
  • No quantitative model of phospho-S28 dynamics across the cycle
  • Functional consequences of UL97 phosphorylation of LIN52 not fully characterized
  • Human disease relevance of the E7-LIN52 axis not established by family/causative genetics

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953897 Cellular responses to stimuli 2
Partners
B-MYB (MYBL2)DYRK1ALIN37LIN9P107P130
Complex memberships
DREAM complexMuvB coreMyb-MuvB (MMB) complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 LIN52 is a component of the mammalian DREAM (DP, RB-like, E2F, and MuvB) complex, which contains p130, E2F4, DP, and MuvB core proteins (LIN9, LIN37, LIN52, LIN54, RBBP4). DREAM binds to more than 800 human promoters in G0 and is required for repression of E2F target genes. In S phase, MuvB proteins (including LIN52) dissociate from p130 and form a distinct submodule that binds MYB. Proteomics (affinity purification/mass spectrometry), ChIP-on-chip genomics, siRNA knockdown, co-immunoprecipitation Molecular cell High 17531812
2011 DYRK1A specifically phosphorylates LIN52 on serine residue 28, and this phosphorylation is required for DREAM complex assembly. Point mutation of S28 or inhibition of DYRK1A disrupts DREAM assembly and reduces the ability of cells to enter quiescence or undergo Ras-induced senescence. Mass spectrometric phosphorylation site identification, in vitro kinase assay, point mutagenesis (S28A), DYRK1A inhibitor treatment, co-immunoprecipitation, cell cycle analysis Genes & development High 21498570
2004 The Drosophila homolog of LIN-52 co-purifies with Myb complex components, E2F2, DP, RBF1, RBF2, L(3)MBT, and Rpd3 (HDAC) to form the Myb-MuvB complex, which localizes to promoters and co-represses transcription of developmentally regulated genes. Affinity chromatography fractionation of Drosophila embryo extracts, co-purification, ChIP, transcriptional reporter assays Genes & development High 15545624
2015 LIN52 contains a sequence that binds directly to the pocket domains of p107 and p130 when phosphorylated at S28 (DYRK1A site). A crystal structure of the LIN52-p107 complex reveals that LIN52 uses a suboptimal LxSxExL sequence together with the phospho-S28 to bind the LxCxE cleft of the pocket domain with high affinity, explaining specificity for p107/p130 over Rb in DREAM. CDK phosphorylation of p130 weakens its LIN52 association, providing a mechanism for DREAM disassembly upon cell cycle entry. Crystal structure determination, in vitro binding assays, mutagenesis, biochemical reconstitution Genes & development High 25917549
2011 LATS2, a Hippo pathway kinase, phosphorylates DYRK1A and enhances DYRK1A's ability to phosphorylate LIN52, thereby promoting DREAM complex assembly and E2F target gene silencing. Reduced LATS2 levels impair DREAM assembly at E2F-regulated promoters. shRNA screen, kinase assay (LATS2 phosphorylation of DYRK1A), ChIP, co-immunoprecipitation Genes & development Medium 21498571
2018 A crystal structure reveals that B-Myb binds MuvB through the adaptor protein LIN52 and the scaffold protein LIN9 to form the Myb-MuvB (MMB) complex. LIN52 serves as the direct binding interface between B-Myb and the MuvB core. Crystal structure determination, biochemical binding assays, domain mapping mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 30224471
2018 Overexpression of B-Myb disrupts DREAM complex assembly in human cells dependent on the intact MuvB-binding domain of B-Myb. Furthermore, B-Myb regulates LIN52 protein expression levels by a mechanism requiring the S28 phosphorylation site in LIN52. Co-immunoprecipitation, western blotting, B-Myb overexpression and MuvB-binding domain mutants, LIN52 S28 point mutant analysis Oncogene Medium 30206359
2022 Within MuvB, LIN9 and LIN37 act as scaffolding proteins that arrange LIN52, LIN54, and RBAP48 for transcription factor, DNA, and histone binding, respectively. MuvB binds nucleosomes through an interface distinct from LIN54-DNA consensus site recognition, and MuvB (including LIN52) increases nucleosome occupancy in a reconstituted promoter; in arrested cells, MuvB primarily associates with the +1 nucleosome near the TSS of MuvB-regulated genes. Crystal structure of MuvB subcomplex, biochemical reconstitution with nucleosomes, ChIP-seq in arrested cells Nature communications High 35082292
2017 The human cytomegalovirus kinase UL97 phosphorylates LIN52, a component of p107- and p130-assembled DREAM complexes, extending viral disruption of cell cycle control to DREAM complex components. In vitro kinase assay, phosphorylation mapping Virology Medium 28946006
2013 DYRK1A-mediated phosphorylation of LIN52 is required for DREAM complex assembly in GIST cells. Depletion of LIN52 inhibits imatinib-induced quiescence and enhances imatinib-induced apoptosis, demonstrating LIN52's role in DREAM-mediated tumor cell quiescence. siRNA knockdown of LIN52, co-immunoprecipitation for DREAM assembly, cell viability and apoptosis assays Cancer research Medium 23786773
2014 In a gene-targeted mouse model uniquely deficient for DREAM assembly (p107 unable to bind MuvB combined with p130 deficiency), cells preferentially assemble BMYB-MuvB and fail to repress transcription. DREAM-deficient mice show defects in endochondral bone formation due to failure of chondrocytes to arrest proliferation. Pharmacologic DYRK kinase inhibition (blocking LIN52 S28 phosphorylation) phenocopies this defect in embryonic bone culture, confirming that DYRK1A phosphorylation of LIN52 is required for DREAM assembly in vivo. Gene-targeted mouse model, micro-CT, histology, DYRK kinase inhibitor treatment of embryonic bone cultures, co-immunoprecipitation Molecular and cellular biology High 24710275
2021 Simultaneous expression of MMB-FOXM1 complex components (including non-phosphorylated LIN52) efficiently bypasses senescence. Non-phosphorylated LIN52 disrupts the DREAM complex, indicating that the phosphorylation state of LIN52 S28 is central to the switch between senescence (DREAM assembled) and proliferation (DREAM disassembled). Senescence bypass assay, overexpression of complex components, co-immunoprecipitation, LIN52 phospho-mutant analysis Scientific reports Medium 34728711
2021 Replacement of the LxSxE motif in LIN52 with LxCxE (LIN52-S20C) increases p130 binding and partially restores DREAM assembly in HPV-positive keratinocytes and human cervical cancer cells, demonstrating that LIN52's LxSxE motif mediates direct binding to p130 and that E7 disrupts this interaction to promote cellular proliferation. LIN52 point mutagenesis (S20C), co-immunoprecipitation, cell proliferation assays in HPV-positive cells Cancers Medium 33513914
2012 Drosophila lin-52 is required for viability and adult eye development. Genetic epistasis shows that lethality and eye defects caused by lin-52 null mutations are suppressed by mutations in other MMB/dREAM subunits, indicating that a partial MMB/dREAM complex lacking Lin-52 is responsible for these phenotypes, and that Lin-52 and Myb counteract the repressive activities of other complex members. P-element excision mutagenesis to generate null alleles, somatic and germ line mutant clone analysis, genetic epistasis (double mutants with other MMB subunits) Molecular and cellular biology Medium 22688510
2014 Drosophila dLin52 is required for transcriptional repression of the pro-apoptotic gene hid in developing photoreceptor neurons. dLin52 cooperates with dRBF and dE2F1/2 for recruitment of the repressor complex at the hid promoter; depletion of dlin52 induces hid expression and apoptosis in eye-antennal discs. RNAi knockdown of dlin52 in Drosophila eye discs, apoptosis assays, ChIP at hid promoter, genetic interaction with dRBF and dE2F mutants Biochimica et biophysica acta Medium 24863159
2003 C. elegans lin-52 is a class B synthetic multivulva (synMuvB) gene that functions in the lin-35 Rb pathway to negatively regulate let-60 ras-mediated vulval induction, suggesting a conserved role for LIN-52 in Rb-mediated signaling. Genetic screen, mutant isolation, epistasis analysis, gene cloning Genetics Medium 12750327
2007 C. elegans lin-52 acts with dpl-1 DP, efl-1 E2F, lin-35 Rb, and lin-37 in transcriptional regulation to promote programmed cell death (killing process), as determined by genetic epistasis in a sensitized ced-3 background. Genetic screen in sensitized ced-3 background, epistasis analysis, cell death scoring Genetics Medium 17237514
2022 In C. elegans, a triple alanine substitution of LIN-52's LxCxE motif severs LIN-35 (Rb)-MuvB association and causes DREAM mutant phenotypes (synthetic multivulva, high-temperature arrest, ectopic germline gene expression in soma). However, disrupting LIN-35-MuvB association did not affect chromatin localization of E2F-DP, LIN-35, or MuvB components, suggesting the E2F-DP-LIN-35 interaction (not LIN-35-MuvB) promotes chromatin localization. CRISPR/Cas9 mutagenesis (LIN-52 LxCxE motif substitution), RNA-seq, ChIP, phenotypic analysis Genetics Medium 35554539
2020 Drosophila Myb protein can bind to C. elegans LIN9-LIN52 proteins in vitro, and amino acids in LIN9 and LIN52 that directly interact with the MuvB-binding domains of human B-Myb and Drosophila Myb are conserved in C. elegans, demonstrating an evolutionarily conserved binding interface on LIN52 for Myb recruitment. In vitro binding assay (Drosophila Myb with C. elegans LIN9-LIN52), mutagenesis of MuvB-binding domain, in vivo synMuv phenotype assay in C. elegans Biology open Medium 32295830
2022 In mouse embryonic stem cells, deficiency of LIN52 (but not LIN9 or LIN37) causes G2/M arrest, loss of pluripotency, and spontaneous differentiation. These phenotypes are partially rescued by ectopic co-expression of Cyclin B1 and Cdk1, placing LIN52 upstream of G2/M regulatory machinery in ESC fate determination. CRISPR/Cas9 knockout, cell cycle analysis, pluripotency marker assays, rescue by Cyclin B1/Cdk1 co-expression The Journal of biological chemistry Medium 35148988

Source papers

Stage 0 corpus · 34 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence. Molecular cell 341 17531812
2011 DYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly. Genes & development 249 21498570
2004 Identification of a Drosophila Myb-E2F2/RBF transcriptional repressor complex. Genes & development 229 15545624
2011 A kinase shRNA screen links LATS2 and the pRB tumor suppressor. Genes & development 108 21498571
2015 Structural mechanisms of DREAM complex assembly and regulation. Genes & development 97 25917549
2013 The DREAM complex mediates GIST cell quiescence and is a novel therapeutic target to enhance imatinib-induced apoptosis. Cancer research 84 23786773
2018 The cell cycle regulatory DREAM complex is disrupted by high expression of oncogenic B-Myb. Oncogene 54 30206359
2016 A Systematic Analysis of Negative Growth Control Implicates the DREAM Complex in Cancer Cell Dormancy. Molecular cancer research : MCR 49 28031411
2020 Genomic Scan for Selection Signature Reveals Fat Deposition in Chinese Indigenous Sheep with Extreme Tail Types. Animals : an open access journal from MDPI 45 32365604
2017 Genome-wide association study and accuracy of genomic prediction for teat number in Duroc pigs using genotyping-by-sequencing. Genetics, selection, evolution : GSE 43 28356075
2003 New genes that interact with lin-35 Rb to negatively regulate the let-60 ras pathway in Caenorhabditis elegans. Genetics 38 12750327
2007 DPL-1 DP, LIN-35 Rb and EFL-1 E2F act with the MCD-1 zinc-finger protein to promote programmed cell death in Caenorhabditis elegans. Genetics 37 17237514
2021 DREAM On: Cell Cycle Control in Development and Disease. Annual review of genetics 36 34496610
2018 Structural mechanism of Myb-MuvB assembly. Proceedings of the National Academy of Sciences of the United States of America 30 30224471
2014 Loss of the mammalian DREAM complex deregulates chondrocyte proliferation. Molecular and cellular biology 27 24710275
2018 MuvB: A Key to Cell Cycle Control in Ovarian Cancer. Frontiers in oncology 25 29942794
2013 The complex containing Drosophila Myb and RB/E2F2 regulates cytokinesis in a histone H2Av-dependent manner. Molecular and cellular biology 24 23438598
2022 The MuvB complex binds and stabilizes nucleosomes downstream of the transcription start site of cell-cycle dependent genes. Nature communications 19 35082292
2020 Genome-wide identification and comparison of differentially expressed profiles of miRNAs and lncRNAs with associated ceRNA networks in the gonads of Chinese soft-shelled turtle, Pelodiscus sinensis. BMC genomics 17 32600250
2021 Restoring the DREAM Complex Inhibits the Proliferation of High-Risk HPV Positive Human Cells. Cancers 16 33513914
2019 An RNAi Screen for Genes Required for Growth of Drosophila Wing Tissue. G3 (Bethesda, Md.) 15 31387856
2017 Phosphorylation of transcriptional regulators in the retinoblastoma protein pathway by UL97, the viral cyclin-dependent kinase encoded by human cytomegalovirus. Virology 14 28946006
2009 Deletion of the p107/p130-binding domain of Mip130/LIN-9 bypasses the requirement for CDK4 activity for the dissociation of Mip130/LIN-9 from p107/p130-E2F4 complex. Experimental cell research 14 19619530
2021 Simultaneous expression of MMB-FOXM1 complex components enables efficient bypass of senescence. Scientific reports 11 34728711
2012 Drosophila lin-52 acts in opposition to repressive components of the Myb-MuvB/dREAM complex. Molecular and cellular biology 9 22688510
2020 A preliminary study of the effect of a high-salt diet on transcriptome dynamics in rat hypothalamic forebrain and brainstem cardiovascular control centers. PeerJ 7 32175184
2020 A long lost key opens an ancient lock: Drosophila Myb causes a synthetic multivulval phenotype in nematodes. Biology open 7 32295830
2022 The MuvB complex safeguards embryonic stem cell identity through regulation of the cell cycle machinery. The Journal of biological chemistry 4 35148988
2011 Dynamic pattern of expression of dlin52, a member of the Myb/MuvB complex, during Drosophila development. Gene expression patterns : GEP 4 22178095
2025 Identification and analysis of diagnostic markers related to lactate metabolism in myocardial infarction. Pathology, research and practice 3 40367892
2022 DREAM interrupted: severing LIN-35-MuvB association in Caenorhabditis elegans impairs DREAM function but not its chromatin localization. Genetics 3 35554539
2021 LIN-35 beyond its classical roles: its function in the stress response. The International journal of developmental biology 2 32930365
2025 Multiple association studies identify 3 novel candidate genes for teat number trait in Danish Landrace and Large White pigs: BRINP3, LIN52, and UBE3B. Journal of animal science 1 40305433
2014 dLin52 is crucial for dE2F and dRBF mediated transcriptional regulation of pro-apoptotic gene hid. Biochimica et biophysica acta 1 24863159

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