Affinage

LIN37

Protein lin-37 homolog · UniProt Q96GY3

Length
246 aa
Mass
28.4 kDa
Annotated
2026-06-10
23 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LIN37 is an essential subunit of the evolutionarily conserved MuvB core complex (with LIN9, LIN52, LIN54, and RBBP4/RBAP48), which assembles with the pocket protein p130, E2F4, and DP1 into the DREAM transcriptional repressor that silences hundreds of cell-cycle-dependent genes during quiescence (PMID:17531812, PMID:28920576). Within MuvB, LIN37 functions as a structural scaffold: it forms a subcomplex with LIN9 that organizes the core for transcription factor, DNA, and histone binding, enabling MuvB to engage and stabilize a tightly positioned +1 nucleosome near the TSS of repressed promoters (PMID:35082292). LIN37 is uniquely required for the repressive output of DREAM—its loss abolishes target-gene repression in G0/G1 even though all other subunits, including p130/p107, remain bound at promoters (PMID:28920576). DREAM assembly depends on DYRK1A-mediated phosphorylation of LIN52 at serine 28, and on cell-cycle entry the MuvB core (including LIN37) dissociates from p130 and instead associates with B-MYB during S phase, a switch that B-MYB overexpression can force prematurely by competing with p130 for the core (PMID:21498570, PMID:30206359). Functionally, LIN37 cooperates with RB to enforce cell-cycle exit and acts as a key effector downstream of p53: in LIN37/RB double-knockout cells, p53-dependent repression of cell-cycle genes and the G1/S checkpoint are lost (PMID:28920576, PMID:31400114). In quiescent cells specifically, LIN37 prevents DNA end resection and homologous recombination by repressing HR genes including BRCA1, BRCA2, PALB2, and RAD51, a function independent of 53BP1 (PMID:34477552). The complex also governs developmental cell-cycle exit, as DREAM loss disrupts chondrocyte proliferation arrest during endochondral bone formation (PMID:24710275), and maintenance of senescence depends on intact DREAM assembly (PMID:34728711). Notably, LIN37 is dispensable for MuvB functions controlling embryonic stem cell self-renewal and G2/M progression, distinguishing its role from that of LIN54 and LIN52 (PMID:35148988).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2006 High

    Established that LIN-37 is a stable member of an Rb-containing multi-subunit synMuvB complex, defining its physical context before its molecular function was known.

    Evidence Co-IP and biochemical fractionation of C. elegans synMuvB mutants

    PMID:17075059

    Open questions at the time
    • Did not assign LIN-37 a discrete molecular role within the complex
    • Mammalian counterpart not yet characterized
  2. 2007 High

    Defined the mammalian DREAM complex and placed LIN37 among the five MuvB-core subunits, showing the complex binds >800 promoters in G0 and that MuvB switches partners between p130 (repression) and MYB (S phase).

    Evidence Proteomics, ChIP, and co-IP in human cells

    PMID:17531812

    Open questions at the time
    • LIN37-specific contribution to repression not isolated
    • Mechanism of nucleosome/promoter engagement unknown
  3. 2011 High

    Showed DREAM assembly—and thus LIN37 incorporation—is gated by DYRK1A phosphorylation of LIN52-S28, linking a kinase signal to repressor formation.

    Evidence Phosphoproteomics, co-IP, LIN52-S28 mutagenesis, and kinase inhibition

    PMID:21498570

    Open questions at the time
    • Does not address LIN37's own regulation or modifications
    • Direct repressive activity of LIN37 not tested
  4. 2017 High

    Isolated LIN37 as the subunit uniquely required for DREAM repression: its loss abolishes target-gene silencing while leaving all other subunits at promoters, and it cooperates with RB to enforce quiescence.

    Evidence Lin37-knockout mouse cells with ChIP, transcriptomics, and Rb/Lin37 double-KO cell-cycle analysis

    PMID:28920576

    Open questions at the time
    • Molecular mechanism by which LIN37 converts a bound complex into a repressive one not resolved
    • Structural basis unknown
  5. 2019 High

    Positioned LIN37 and RB as the key effectors through which p53 represses cell-cycle genes, since their joint loss abrogates p53-dependent repression and the G1/S checkpoint.

    Evidence CRISPR single/double knockouts of LIN37 and RB with RNA-seq and cell-cycle analysis

    PMID:31400114

    Open questions at the time
    • Connection between p53 signaling and DREAM assembly mechanistically undefined
    • Direct vs indirect coupling to p53 unclear
  6. 2021 High

    Revealed a quiescence-specific genome-protective role: LIN37/DREAM represses HR genes to block DNA end resection and homologous recombination in G0, independent of 53BP1.

    Evidence LIN37-knockout cells with resection/HR assays, RAD51 foci, and epistasis with 53BP1 and BRCA1

    PMID:34477552

    Open questions at the time
    • Why this role is restricted to G0 and not cycling G1 not fully explained
    • No structural detail on HR-gene promoter engagement
  7. 2022 High

    Provided the structural basis for LIN37 function, showing it forms a LIN9-LIN37 scaffold organizing the MuvB core and enabling nucleosome binding and stabilization of the +1 nucleosome at repressed promoters.

    Evidence Crystal structure of a LIN9-LIN37 subcomplex, in vitro nucleosome-binding and promoter reconstitution, and ChIP-seq in arrested cells

    PMID:35082292

    Open questions at the time
    • How nucleosome stabilization mechanistically silences transcription not fully resolved
    • Structure of full MuvB or DREAM not determined
  8. 2022 Medium

    Distinguished LIN37 from other MuvB subunits by showing it is dispensable for ESC self-renewal and G2/M progression, unlike LIN54 and LIN52.

    Evidence CRISPR knockout of individual MuvB components in mouse ESCs with cell-cycle and pluripotency readouts

    PMID:35148988

    Open questions at the time
    • Does not explain the molecular basis of LIN37's context-specific dispensability
    • Negative finding limited to ESC context

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LIN37 mechanistically converts a promoter-bound MuvB core into an active repressive state—and whether its own regulation links DREAM to specific upstream signals—remains unresolved.
  • No defined post-translational regulation of LIN37 itself
  • Mechanism connecting +1 nucleosome stabilization to transcriptional silencing incomplete
  • No structure of LIN37 within full DREAM

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0005198 structural molecule activity 1 GO:0042393 histone binding 1 GO:0060090 molecular adaptor activity 1
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-4839726 Chromatin organization 1 R-HSA-73894 DNA Repair 1
Partners
B-MYBE2F4LIN52LIN54LIN9P130RBBP4
Complex memberships
DREAM complexMuvB core complex

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 LIN-37 (mammalian homolog Mip40/LIN37) is a core subunit of the DREAM complex (DP, RB-like, E2F, and MuvB), which contains p130, E2F4, DP1, and five MuvB-like 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 LIN37) dissociate from p130 and form a distinct submodule that binds MYB. Proteomics (mass spectrometry), genomics, co-immunoprecipitation, ChIP Molecular cell High 17531812
2006 C. elegans LIN-37 is a component of a multi-subunit complex containing LIN-35 (Rb homolog) and at least seven synMuvB proteins. Biochemical analyses of mutants showed that LIN-9, LIN-53, and LIN-54 are required for stable formation of this complex. This LIN-35-containing complex is distinct from a second NuRD-like synMuvB complex. Co-immunoprecipitation, biochemical fractionation of C. elegans mutants Proceedings of the National Academy of Sciences of the United States of America High 17075059
1995 C. elegans LIN-37 acts cell non-autonomously and plays a role, together with LIN-15, in the generation of an intercellular signal by hyp7 that represses vulval development, as demonstrated by mosaic analysis. Genetic mosaic analysis using ncl-1 cell-autonomous marker Genetics Medium 8582642
2011 LIN37 is a stable core component of the MuvB complex in DREAM. The MuvB core (including LIN37) dissociates from p130 upon cell cycle entry and associates with BMYB during S phase. DYRK1A-mediated phosphorylation of LIN52 at serine 28 is required for DREAM assembly, and thus indirectly for LIN37 incorporation into DREAM. Mass spectrometry phosphoproteomic analysis, co-immunoprecipitation, point mutagenesis of LIN52-S28, kinase inhibition Genes & development High 21498570
2009 Mip40/LIN-37 is part of the Mip Core Complex (MCC/LINC) with Mip130/LIN-9, Mip120/LIN-54, and Sin3b, which is detectable in all phases of the cell cycle. This core complex recruits p107, p130, E2F4, and HDAC1 in G0/G1 and B-Myb in S-phase. CDK4-mediated phosphorylation of pocket proteins (p107/p130) mediates the switch from repressor to activator complexes. Co-immunoprecipitation, deletion mutant analysis, CDK4-/- MEF rescue Experimental cell research Medium 19619530
2017 LIN37 is an essential functional component of the mammalian DREAM complex. Mouse cells lacking Lin37 proliferate normally, but DREAM completely loses its ability to repress target genes in G0/G1 even though all other subunits (including p130/p107) still bind to target gene promoters. Cells lacking both Rb and Lin37 are incapable of exiting the cell cycle, demonstrating that Lin37 cooperates with Rb to induce quiescence. Lin37 knockout mouse cells, ChIP, gene expression analysis, cell cycle analysis eLife High 28920576
2004 C. elegans LIN-37 genetically cooperates with LIN-35/Rb and LIN-9 (class B synMuv proteins) together with the SWI/SNF component PSA-1/SWI3 to regulate asymmetric T cell division and larval development. Loss-of-function mutations in lin-37 strongly enhanced defects in asymmetric T cell division caused by psa-1 mutation. Genetic epistasis (double mutant analysis), C. elegans developmental phenotype Genetics Medium 15280233
2007 C. elegans LIN-37 (Mip40 homolog) participates in transcriptional regulation of programmed cell death, acting together with DPL-1/DP, EFL-1/E2F, LIN-35/Rb, and LIN-52 to promote programmed cell death in C. elegans. Genetic epistasis, sensitized mutant screen (ced-3 partial loss-of-function background) Genetics Medium 17237514
2019 Knockout of LIN37/DREAM results in reduced repression of cell-cycle genes after p53 activation. In LIN37-/-;RB-/- double-knockout cells, p53-dependent repression of cell-cycle genes is completely abrogated, leading to loss of the G1/S checkpoint. LIN37 and RB together are key effectors of the p53 signaling pathway for downregulating cell-cycle genes. CRISPR/Cas9 knockout of LIN37 and RB, RNA-seq, cell cycle analysis Nucleic acids research High 31400114
2018 B-Myb overexpression disrupts the DREAM complex in human cells through its MuvB-binding domain, competing with p130 for MuvB core (including LIN37) binding. High B-Myb expression correlates with global loss of repression of DREAM target genes. Co-immunoprecipitation, B-Myb MuvB-binding domain mutant analysis, gene expression profiling Oncogene Medium 30206359
2014 LIN37 is a component of the mammalian DREAM complex required for cell cycle exit in chondrocytes during endochondral bone formation. Mice with targeted disruption of MuvB binding to p107/p130 (lacking functional DREAM) show defects in chondrocyte proliferation arrest and die shortly after birth. DYRK kinase inhibition phenocopies DREAM loss in embryonic bone cultures. Gene-targeted mouse model (p107 MuvB-binding domain disruption + p130 knockout), histology, micro-CT, pharmacologic DYRK inhibition in embryonic bone cultures Molecular and cellular biology High 24710275
2021 LIN37, as a component of the DREAM transcriptional repressor complex, prevents DNA end resection and homologous recombination (HR) in quiescent (G0) cells by repressing expression of HR proteins including BRCA1, BRCA2, PALB2, and RAD51. This function is independent of 53BP1. Loss of LIN37 in G0 cells leads to BRCA1-dependent DNA end resection, RAD51 filament formation, and HR. LIN37 is not required for DNA end protection in cycling cells at G1 phase. LIN37 knockout cells, DNA end resection assays, HR assays, epistasis with 53BP1 and BRCA1 knockdown, RAD51 foci analysis, gene expression analysis eLife High 34477552
2022 LIN37 functions as a scaffolding protein within the MuvB complex, arranging LIN9, LIN52, LIN54, and RBAP48 for transcription factor, DNA, and histone binding. Crystal structure of a LIN9-LIN37 subcomplex reveals that these two subunits form the structural scaffold of MuvB. MuvB binds nucleosomes through an interface distinct from the LIN54-DNA consensus site and increases nucleosome occupancy in reconstituted promoters; in arrested cells MuvB associates with a tightly positioned +1 nucleosome near the TSS. Crystal structure determination, in vitro nucleosome binding assays, promoter reconstitution, ChIP-seq in arrested cells Nature communications High 35082292
2019 In C. elegans synMuvB mutants (including lin-37), germline and synMuvB target genes show dramatic reduction of H3K9me2 at their promoters. However, the reduction of H3K9me2 in lin-37 mutants is much weaker than in lin-15B mutants, suggesting that LIN-37/DREAM and LIN-15B use distinct molecular mechanisms for gene repression, with H3K9me2 being primarily driven by LIN-15B rather than LIN-37. ChIP-seq for H3K9me2 in C. elegans synMuvB mutants Genetics Medium 30910798
2021 Simultaneous expression of MMB-FOXM1 components bypasses senescence; non-phosphorylated LIN52 (which disrupts DREAM complex assembly, releasing LIN37 and other MuvB components) is a crucial component for this bypass, indicating that DREAM complex assembly (including LIN37 as a core component) is central to maintaining senescence. Stable senescence bypass assay in conditional immortalized human breast fibroblasts, DREAM assembly disruption via LIN52 phospho-mutants Scientific reports Medium 34728711
2022 In mouse embryonic stem cells, deficiency of Lin37 does not trigger G2/M arrest or loss of pluripotency (in contrast to deficiency of Lin54 or Lin52 which do cause these phenotypes), indicating that Lin37 is dispensable for the MuvB complex functions controlling ESC self-renewal and G2/M progression. CRISPR/Cas9 knockout of individual MuvB components in ESCs, cell cycle analysis, pluripotency marker analysis The Journal of biological chemistry Medium 35148988
2024 C. elegans LIN-37, as a component of the DREAM complex (together with LIN-35 and LIN-54), is required for temperature stress-induced increases in germline apoptosis and for DNA damage-induced apoptosis. LIN-37 mutants fail to upregulate germline apoptosis under moderate temperature stress, and this pathway depends on repression of CED-9/Bcl2 function. C. elegans lin-37 mutant analysis, germline apoptosis quantification under temperature stress and DNA damage conditions, genetic epistasis with ced-9 bioRxivpreprint Medium bio_10.1101_2024.11.13.623436

Source papers

Stage 0 corpus · 23 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
2006 Some C. elegans class B synthetic multivulva proteins encode a conserved LIN-35 Rb-containing complex distinct from a NuRD-like complex. Proceedings of the National Academy of Sciences of the United States of America 121 17075059
1995 The ncl-1 gene and genetic mosaics of Caenorhabditis elegans. Genetics 102 8582642
2019 DREAM and RB cooperate to induce gene repression and cell-cycle arrest in response to p53 activation. Nucleic acids research 94 31400114
2019 TERC promotes cellular inflammatory response independent of telomerase. Nucleic acids research 62 31294790
2018 The cell cycle regulatory DREAM complex is disrupted by high expression of oncogenic B-Myb. Oncogene 54 30206359
2004 lin-35/Rb cooperates with the SWI/SNF complex to control Caenorhabditis elegans larval development. Genetics 43 15280233
2017 The DREAM complex through its subunit Lin37 cooperates with Rb to initiate quiescence. eLife 42 28920576
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
2019 Repression of Germline Genes in Caenorhabditis elegans Somatic Tissues by H3K9 Dimethylation of Their Promoters. Genetics 27 30910798
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
2021 LIN37-DREAM prevents DNA end resection and homologous recombination at DNA double-strand breaks in quiescent cells. eLife 21 34477552
2022 The MuvB complex binds and stabilizes nucleosomes downstream of the transcription start site of cell-cycle dependent genes. Nature communications 19 35082292
2022 RBL2/DREAM-mediated repression of the Aurora kinase A/B pathway determines therapy responsiveness and outcome in p53 WT NSCLC. Scientific reports 15 35058503
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
2023 c-MYC-Induced AP4 Attenuates DREAM-Mediated Repression by p53. Cancers 7 36831504
2022 The MuvB complex safeguards embryonic stem cell identity through regulation of the cell cycle machinery. The Journal of biological chemistry 4 35148988
2025 The Tumor Suppressor p53 Downregulates p107 (RBL1) Through p21-RB/E2F Signaling and Tandem E2F Sites. International journal of molecular sciences 1 41155196
2026 Novel transcriptomic alterations in poorly differentiated endometrial carcinomas: evidence from South African women. Frontiers in oncology 0 41952686

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