Affinage

MXD1

Max dimerization protein 1 · UniProt Q05195

Length
221 aa
Mass
25.3 kDa
Annotated
2026-04-29
100 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MXD1 (MAD1) is a bHLH-leucine zipper transcriptional repressor that functions as a central antagonist of MYC-driven transcription, coupling growth factor signaling to cell cycle exit, differentiation, and control of ribosome biogenesis. MXD1 heterodimerizes with MAX to bind E-box (CACGTG) sequences, displacing MYC:MAX activating complexes at target promoters including hTERT, PTEN, UBF, and rDNA loci, and recruits the Sin3/HDAC corepressor complex via its N-terminal SIN3-interaction domain (SID), with additional requirement for Ski and PML as corepressor components (PMID:8224841, PMID:8754821, PMID:10049357, PMID:10723141, PMID:15282543, PMID:28543796). MXD1 expression is induced upon myeloid, adipocytic, and dendritic cell differentiation, where it replaces MYC:MAX complexes and suppresses proliferative and biosynthetic gene programs; its loss impairs lineage-specific differentiation including megakaryocyte commitment and cDC1 maturation (PMID:8224841, PMID:10797315, PMID:32071205, PMID:27520398). MXD1 protein stability is negatively regulated by RSK/S6K-mediated phosphorylation at Ser145, which triggers ubiquitination and proteasomal degradation, and by FBW7 E3-ubiquitin ligase activity, while vitamin D signaling stabilizes MXD1 protein (PMID:18451027, PMID:23112173).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1993 High

    The identity of the MYC-antagonizing partner for MAX during differentiation was unknown; co-IP from differentiating U937 monocytes revealed that MAD1:MAX heterodimers replace MYC:MAX complexes upon TPA-induced differentiation, establishing the Myc/Max/Mad switching paradigm.

    Evidence Co-immunoprecipitation and gel-shift assays from differentiating U937 cells

    PMID:8224841

    Open questions at the time
    • Mechanism by which differentiation signals induce MAD1 expression was not defined
    • Identity of MAD1 target genes was unknown
    • Whether MAD1 is required for differentiation (vs. sufficient) was not tested
  2. 1995 High

    The domains required for MAD1's tumor-suppressive function were undefined; deletion mutagenesis in transformation assays showed that MAD1 blocks MYC-RAS cotransformation through three separable requirements: DNA-binding basic region, leucine zipper for MAX dimerization, and an N-terminal domain for mSin3 corepressor interaction.

    Evidence Focus formation assays with MAD1 deletion mutants in rat embryo fibroblasts

    PMID:7669717

    Open questions at the time
    • Direct biochemical characterization of the Sin3 interaction was not yet performed
    • Whether transformation suppression reflects transcriptional repression or other functions was not resolved
  3. 1996 High

    How MAD1 executes transcriptional repression was unclear; two studies established that MAD1's SID directly binds the PAH2 domain of Sin3, recruiting the Sin3/HDAC corepressor complex to E-box promoters, and that this repressive activity is essential for MAD1's ability to inhibit G1-to-S cell cycle progression.

    Evidence Yeast two-hybrid and in vitro binding for Sin3 interaction; FACS cell cycle analysis with repressor-dead mutants in 3T3 cells

    PMID:8649388 PMID:8754821

    Open questions at the time
    • The full composition of the MAD1-recruited corepressor complex was not defined
    • Specific transcriptional targets mediating cell cycle arrest were unknown
  4. 1999 High

    The role of additional corepressor subunits in MAD1-mediated repression was unresolved; identification of Ski as a required component of the Sin3/HDAC complex, validated by ectopic ornithine decarboxylase expression in ski-null embryos, expanded the corepressor machinery necessary for MAD1 function.

    Evidence Co-IP, transcriptional reporters, ski-knockout mouse embryo analysis

    PMID:10049357

    Open questions at the time
    • Whether Ski is required at all MAD1 target genes or a subset was not determined
    • Structural basis of Ski–Sin3 interaction in the context of MAD1 was unknown
  5. 2000 High

    Direct transcriptional targets of MAD1 were largely unknown; three studies identified hTERT as a direct MAD1 target via E-box-dependent repression, showed that MAD1 inhibits both proliferation and Fas/TRAIL-induced apoptosis, and demonstrated that MAD1 blocks the proliferative burst required for adipocyte differentiation.

    Evidence hTERT promoter reporter mutagenesis; inducible MAD1 expression in U2OS cells with apoptosis assays; BrdU/FACS in 3T3-L1 adipogenic differentiation

    PMID:10723141 PMID:10744730 PMID:10797315

    Open questions at the time
    • Mechanism of apoptosis inhibition (whether transcription-dependent) was not fully clarified
    • Genome-wide target identification was not performed
  6. 2001 High

    Whether PML bodies contribute to MAD1-mediated repression was untested; PML was shown to interact with Sin3A, Ski, N-CoR, and HDAC1 and to be required for MAD1-mediated transcriptional repression, while PML-RARα disrupted this complex.

    Evidence Co-immunoprecipitation and transcriptional reporter assays

    PMID:11430826

    Open questions at the time
    • Whether PML acts at all MAD1 targets or specifically at certain promoters was not resolved
    • In vivo relevance in leukemia beyond reporter assays was not tested
  7. 2002 High

    Whether MAD1 and MYC differ in intrinsic DNA-binding specificity was unclear; SELEX demonstrated identical E-box preferences in vitro, but chimeric MYC-MAD1 bHLHZ proteins could promote growth but not apoptosis, indicating in vivo functional divergence beyond DNA binding.

    Evidence SELEX and chimeric protein functional assays

    PMID:12149476

    Open questions at the time
    • What determines differential in vivo target selection was not identified
    • Role of cofactor recruitment in target discrimination was not addressed
  8. 2003 High

    The atomic basis of MAD1:MAX heterodimerization and E-box recognition was unknown; the 2.0 Å crystal structure revealed structural differences in the leucine zipper explaining preferential heterodimerization and showed that, unlike MYC:MAX, MAD1:MAX does not form bivalent heterotetramers.

    Evidence X-ray crystallography at 2.0 Å resolution

    PMID:12553908

    Open questions at the time
    • Structure of full-length MAD1 including the SID in complex with Sin3 was not obtained
    • How structural differences translate to chromatin-level function was not addressed
  9. 2004 High

    Whether MAD1 regulates ribosome biogenesis was untested; ChIP and nuclear run-on in granulocytic cells showed MAD1 represses rDNA transcription by targeting the UBF promoter, and MAD1-deficient cells exhibited increased cell volume and protein synthesis, establishing a role in cell growth control.

    Evidence ChIP, nuclear run-on, siRNA knockdown, MAD1-deficient granulocytic cells

    PMID:15282543

    Open questions at the time
    • Whether MAD1 directly binds rDNA promoters in addition to UBF was not distinguished
    • Contribution to ribosome biogenesis in non-myeloid lineages was not assessed
  10. 2008 High

    How growth factor signaling eliminates MAD1 protein was unknown; RSK and S6K were identified as kinases that phosphorylate MAD1 at Ser145 downstream of PI3K and MAPK, triggering its ubiquitination and proteasomal degradation and thereby relieving repression of MYC target genes.

    Evidence In vitro kinase assays, S145A mutagenesis, ubiquitination and proteasome inhibitor experiments

    PMID:18451027

    Open questions at the time
    • The E3 ubiquitin ligase responsible for Ser145-dependent degradation was not identified in this study
    • Whether other phosphorylation sites contribute to stability regulation was not tested
  11. 2012 High

    The E3 ligase controlling MAD1 turnover and the role of vitamin D signaling were unresolved; FBW7 was identified as the ubiquitin ligase regulating both MXD1 and c-MYC stability, and vitamin D/VDR signaling was shown to stabilize MXD1 while destabilizing c-MYC, with FBW7 ablation attenuating this regulation.

    Evidence FBW7 knockdown, protein stability assays, VDR-knockout mouse model, mathematical modeling

    PMID:23112173

    Open questions at the time
    • Whether FBW7 recognizes a phosphodegron created by Ser145 phosphorylation specifically was not tested
    • Tissue-specific regulation of this axis in vivo was not fully characterized
  12. 2016 Medium

    Whether MXD1 influences hematopoietic lineage decisions beyond monocyte differentiation was untested; knockdown in CD34+ progenitors favored granulocyte expansion at the expense of megakaryocyte commitment, establishing MXD1 as a lineage-choice regulator in myelopoiesis.

    Evidence siRNA knockdown in CD34+ cells, lineage differentiation assays, luciferase reporter validation as miR-382-5p target

    PMID:27520398

    Open questions at the time
    • Target genes mediating megakaryocyte vs. granulocyte fate decision were not identified
    • Whether this reflects MYC antagonism specifically was not demonstrated
  13. 2017 Medium

    MXD1's role under hypoxia was unexplored; ChIP and reporter assays showed MXD1 directly represses PTEN via E-box binding under hypoxic conditions, activating PI3K/AKT signaling and conferring cisplatin resistance in osteosarcoma.

    Evidence ChIP, luciferase reporter, siRNA knockdown in osteosarcoma cells under hypoxia

    PMID:28543796

    Open questions at the time
    • Whether hypoxic PTEN repression is a general MXD1 function or cell-type specific was not assessed
    • MXD1 acting as a repressor of a tumor suppressor complicates the simple tumor-suppressive model and was not reconciled
  14. 2020 Medium

    The in vivo role of MXD1 in immune cell maturation was uncharacterized; Mxd1 knockout mice showed that MXD1 is required in mature cDC1 dendritic cells to repress the MYCL-driven biosynthetic program, and separately, the MXD1 SID was shown to be a potent transcriptional repressor domain when used in CRISPRi.

    Evidence Mxd1 and Mycl knockout mice with gene expression profiling; CRISPRi library screening in lymphoid cells

    PMID:32071205 PMID:32156728

    Open questions at the time
    • Specific MXD1 target genes in cDC1 maturation were not defined
    • Whether the SID CRISPRi phenotype reflects endogenous MXD1 repression mechanisms fully was not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • A comprehensive genome-wide map of direct MXD1 target genes across differentiation states, the structural basis for the full SID:Sin3:HDAC corepressor assembly, and the in vivo consequences of MXD1 loss in solid tissues remain to be established.
  • No genome-wide ChIP-seq or CUT&RUN map of MXD1 binding across multiple cell types has been reported in the timeline
  • Full-length MXD1:MAX:Sin3:HDAC complex structure is lacking
  • Conditional tissue-specific knockout phenotypes have not been described beyond immune lineages

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 1 GO:0005654 nucleoplasm 1
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1266738 Developmental Biology 4 R-HSA-4839726 Chromatin organization 4 R-HSA-162582 Signal Transduction 2 R-HSA-1640170 Cell Cycle 2 R-HSA-392499 Metabolism of proteins 2
Partners
FBW7HDAC1HDAC2MAXPMLSIN3ASKI
Complex memberships
MAD1:MAX heterodimerSin3/HDAC corepressor complexSin3A/N-CoR/Ski/HDAC complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 MAD1 (Mad) protein forms heterodimers with Max in vivo during monocyte/macrophage differentiation. In undifferentiated U937 cells, Max is complexed with Myc; upon TPA-induced differentiation, Mad:Max complexes replace Myc:Max complexes, demonstrating a switch in Max heterocomplex composition accompanying differentiation. Co-immunoprecipitation from differentiating U937 cells; gel shift/DNA-binding assays Genes & development High 8224841
1996 MAD1 (Mad1) inhibits cell cycle progression from G1 to S phase when ectopically expressed in 3T3 cells, and this antiproliferative activity is tightly coupled to its function as a transcriptional repressor (repressor-dead mutants lose cell cycle inhibitory activity). Ectopic expression in 3T3 cells, cell cycle analysis by FACS, transcriptional repression assays with mutants Molecular and cellular biology High 8649388
1995 MAD1 blocks oncogenic transformation (Myc-Ras cotransformation) through multiple protein-protein interactions requiring: (1) an intact DNA-binding basic region, (2) the leucine zipper (for Max dimerization), and (3) an N-terminal domain for interaction with mSin3 corepressor. Focus formation transformation assays with Mad1 deletion mutants in rat embryo fibroblasts Cell growth & differentiation High 7669717
1996 MAD1 represses transcription through direct interaction of its N-terminal SIN3-interaction domain (SID) with the PAH2 domain of Sin3 (yeast ySin3/mammalian mSin3), recruiting Sin3 to promoters via DNA-bound Mad1:Max heterodimers. Yeast two-hybrid, in vitro binding, transcriptional repression reporter assays in sin3 mutant yeast Molecular and cellular biology High 8754821
1999 Ski protein is a component of the N-CoR/SMRT/mSin3/HDAC complex and is required for transcriptional repression mediated by Mad (MAD1). The oncogenic v-Ski, lacking the mSin3A-binding domain, acts in a dominant-negative fashion abrogating Mad-mediated repression. In ski-deficient mouse embryos, the Mad-Max target gene ornithine decarboxylase is ectopically expressed. Co-immunoprecipitation, transcriptional reporter assays, ski-knockout mouse embryo analysis Genes & development High 10049357
2001 PML interacts with multiple corepressors (c-Ski, N-CoR, mSin3A) and HDAC1, and this interaction is required for transcriptional repression mediated by MAD1. PML-RARalpha disrupts corepressor complex function and inhibits Mad-mediated repression. Co-immunoprecipitation, transcriptional repression reporter assays Molecular cell High 11430826
2003 Crystal structures of Mad-Max bHLHZ domain heterodimer bound to E-box DNA (5'-CACGTG-3') at 2.0 Å resolution reveal that Mad-Max resembles the symmetric Max homodimer with structural differences in the coiled-coil leucine zipper region explaining preferential heterodimerization. Unlike Myc-Max, Mad-Max does not dimerize to form a bivalent heterotetramer. X-ray crystallography at 2.0 Å resolution Cell High 12553908
2000 MAD1 (Mad) was identified as a direct transcriptional repressor of the hTERT (telomerase catalytic subunit) gene promoter. Mutation of Mad E-box DNA binding sites in the hTERT promoter caused de-repression, and this Mad-mediated repression was counteracted by ectopic Myc expression. Expression cloning screen, reporter gene assays with promoter mutants, endogenous hTERT promoter analysis Oncogene High 10723141
2004 MAD1 represses rDNA transcription by interacting directly with the promoter of upstream binding factor (UBF), an rDNA regulatory factor, in granulocytic cells. Granulocytic cells deficient in MAD1 display increased cell volume, rDNA transcription and protein synthesis, demonstrating MAD1 regulates ribosome biogenesis and cell growth. Nuclear run-on assays, chromatin immunoprecipitation (ChIP), siRNA knockdown of UBF, MAD1-deficient cells The EMBO journal High 15282543
2008 MAD1 protein is phosphorylated on serine 145 by p90 RSK and p70 S6 kinase downstream of PI3K/Akt and MAPK pathways upon serum or insulin stimulation. This phosphorylation accelerates ubiquitination and proteasomal degradation of MAD1, thereby promoting Myc transcriptional activity. In vitro kinase assays, site-directed mutagenesis (S145A), ubiquitination assays, proteasome inhibitor experiments Proceedings of the National Academy of Sciences of the United States of America High 18451027
2000 MAD1 inhibits both cell proliferation and apoptosis. When induced in U2OS cells, MAD1 localizes to the nucleus, binds DNA as a Max heterodimer, reduces cellular growth, and interferes with Fas-, TRAIL-, and UV-induced apoptosis by reducing caspase-8 activation during Fas-mediated apoptosis. Tetracycline-regulated expression system in U2OS cells, apoptosis assays, caspase-8 activation measurement, microinjection experiments The Journal of biological chemistry High 10744730
2002 MAD1 and Myc bHLHZ domains have identical intrinsic DNA-binding specificities in vitro (both select CACGTG E-boxes), yet a chimeric Myc protein with the Mad1 bHLHZ domain can recapitulate Myc growth-promoting activity but not apoptotic function, indicating non-identical target gene sets in vivo. SELEX (selection and amplification of randomized oligonucleotides), chimeric protein functional assays Proceedings of the National Academy of Sciences of the United States of America High 12149476
2010 Kinetic analysis reveals that Mad:Max heterodimer formation has a rate constant approximately 2-fold lower than Myc:Max dimerization, and both dimerization and DNA-binding rates are concentration-independent (suggesting rate-limiting conformational changes). The monomer pathway (sequential binding to DNA) is kinetically favored over the pre-formed dimer pathway. Stopped-flow fluorescence polarization, Arrhenius activation energy analysis Biochemistry Medium 20170194
2012 Vitamin D receptor (VDR) and 1,25-dihydroxyvitamin D (1,25D) regulate MXD1 expression and stability: 1,25D enhances MXD1 expression and protein stability, while inhibiting c-MYC expression and accelerating its turnover. F-box protein FBW7 (E3-ubiquitin ligase) controls stability of both c-MYC and MXD1; FBW7 ablation attenuates 1,25D regulation of both proteins. Cell-based and animal studies, protein stability assays, FBW7 knockdown, mathematical modeling, mouse VDR-knockout analysis Proceedings of the National Academy of Sciences of the United States of America High 23112173
2011 Solution NMR structure of the mSin3A PAH2 domain bound to the SID1 motif of Pf1 reveals structural features reminiscent of the Mad1/Mxd1:Sin3 interaction. The MRG15 subunit competes with Sin3 for binding to the same Pf1 segment containing SID1, showing competitive regulation within the repressor complex. NMR structure determination, binding assays, mutagenesis Journal of molecular biology High 21440557
2003 p53 represses MAD1 (mitotic checkpoint MAD1) transcription through a 38-bp p53-responsive element in the MAD1 promoter. Repression involves recruitment of HDAC1 and co-repressor mSin3a to the MAD1 promoter (shown by ChIP), and is relieved by the HDAC inhibitor trichostatin A. Promoter truncation/reporter assays, chromatin immunoprecipitation (ChIP), trichostatin A treatment The Journal of biological chemistry Medium 12876282
2015 MXD1 binds to the Sin3A repressor protein complex through increased association with HDAC-2, and directly binds E-box sites within the hTERT promoter to repress telomerase activity. This was demonstrated after miR-202 downregulation increases Mxd1 expression. ChIP at hTERT promoter, co-immunoprecipitation with Sin3A/HDAC-2, HDAC activity assay, telomerase activity assay Cancer biology & therapy Medium 25611699
2017 MXD1 directly binds E-box sites within the PTEN promoter to repress PTEN expression under hypoxia (confirmed by luciferase reporter and ChIP assays), leading to activation of PI3K/AKT signaling and cisplatin resistance in osteosarcoma cells. Luciferase reporter assay, chromatin immunoprecipitation (ChIP), siRNA knockdown, PI3K/AKT signaling analysis Molecular carcinogenesis Medium 28543796
2020 The SIN3-interaction domain (SID) derived from MXD1 protein functions as a highly effective transcriptional repressor domain when fused to dCas9 (CRISPRi), superior to the KRAB repressor domain in lymphoid cell lines, demonstrating the potency of the MXD1 SID in mediating transcriptional repression. CRISPRi library screening, competition assays, RT-qPCR, ChIP for MYC at target promoters Proceedings of the National Academy of Sciences of the United States of America Medium 32156728
2020 MYCL and MXD1 regulate a shared but reciprocal transcriptional program during cDC1 (classical dendritic cell) maturation. MXD1 is induced in mature cDC1s (concomitant with repression of Mycl), and Mxd1-/- mature cDC1s exhibit impaired ability to inhibit the biosynthetic transcriptional signature supported by MYCL. Mxd1 and Mycl knockout mouse models, gene expression profiling Proceedings of the National Academy of Sciences of the United States of America Medium 32071205
2000 During adipocytic differentiation of 3T3-L1 cells, ectopic expression of Mad1 inhibits S phase entry and the proliferative burst, consequently inhibiting adipocytic differentiation. Mad4 and Mad1 are induced during late differentiation, while Mad3 is associated with S phase progression. Ectopic expression, BrdU incorporation, FACS cell cycle analysis, adipogenic differentiation assay Journal of cellular physiology Medium 10797315
2016 MXD1 knockdown in CD34+ hematopoietic stem/progenitor cells mimics the effect of miR-382-5p overexpression, favoring granulocyte expansion and impairing megakaryocyte commitment, establishing MXD1 as a functional mediator of lineage choice in myelopoiesis. MXD1 was validated as a direct target of miR-382-5p by luciferase reporter assay. siRNA knockdown of MXD1, luciferase reporter assay, lineage differentiation assays from CD34+ cells Stem cells and development Medium 27520398

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 The Myc/Max/Mad network and the transcriptional control of cell behavior. Annual review of cell and developmental biology 1083 11031250
1996 MADR1, a MAD-related protein that functions in BMP2 signaling pathways. Cell 628 8653785
1996 A human Mad protein acting as a BMP-regulated transcriptional activator. Nature 587 8637600
1997 Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic. Nature 459 9230443
2003 X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors. Cell 445 12553908
1998 Human T cell leukemia virus type 1 oncoprotein Tax targets the human mitotic checkpoint protein MAD1. Cell 433 9546394
1993 A switch from Myc:Max to Mad:Max heterocomplexes accompanies monocyte/macrophage differentiation. Genes & development 289 8224841
1994 Myc-Max-Mad: a transcription factor network controlling cell cycle progression, differentiation and death. Current opinion in genetics & development 287 8193530
2002 Adipogenesis and aging: does aging make fat go MAD? Experimental gerontology 273 12175476
1999 TGF-beta family signal transduction in Drosophila development: from Mad to Smads. Developmental biology 264 10357889
1999 Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor. Genes & development 243 10049357
2008 Activation of PI3K/Akt and MAPK pathways regulates Myc-mediated transcription by phosphorylating and promoting the degradation of Mad1. Proceedings of the National Academy of Sciences of the United States of America 203 18451027
2001 Function and regulation of the transcription factors of the Myc/Max/Mad network. Gene 194 11602341
2007 Heterozygous deletion of mitotic arrest-deficient protein 1 (MAD1) increases the incidence of tumors in mice. Cancer research 154 17210695
2004 MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation. The EMBO journal 152 15282543
2012 Meta-analysis derived (MAD) transcriptome of psoriasis defines the "core" pathogenesis of disease. PloS one 150 22957057
1995 Regulation of Myc and Mad during epidermal differentiation and HPV-associated tumorigenesis. Oncogene 145 8545105
2003 Nuf2 and Hec1 are required for retention of the checkpoint proteins Mad1 and Mad2 to kinetochores. Current biology : CB 139 14654001
2011 Constitutive Mad1 targeting to kinetochores uncouples checkpoint signalling from chromosome biorientation. Nature cell biology 138 21394085
2000 Identification of Mad as a repressor of the human telomerase (hTERT) gene. Oncogene 138 10723141
1997 Identification of Smad2, a human Mad-related protein in the transforming growth factor beta signaling pathway. The Journal of biological chemistry 138 9006934
2001 Mad2 binding to Mad1 and Cdc20, rather than oligomerization, is required for the spindle checkpoint. The EMBO journal 136 11707408
2001 Role of PML and PML-RARalpha in Mad-mediated transcriptional repression. Molecular cell 125 11430826
2011 Cooperative regulation of growth by Yorkie and Mad through bantam. Developmental cell 120 21238929
1996 Inhibition of cell proliferation by the Mad1 transcriptional repressor. Molecular and cellular biology 118 8649388
2002 Spindle checkpoint requires Mad1-bound and Mad1-free Mad2. Molecular biology of the cell 115 12006648
1999 Taking MAD to the extreme: ultrafast protein structure determination. Acta crystallographica. Section D, Biological crystallography 111 10329779
1998 Sequential expression of the MAD family of transcriptional repressors during differentiation and development. Oncogene 108 9519870
2004 NEK2A interacts with MAD1 and possibly functions as a novel integrator of the spindle checkpoint signaling. The Journal of biological chemistry 106 14978040
2014 MiR-19a/b modulate the metastasis of gastric cancer cells by targeting the tumour suppressor MXD1. Cell death & disease 104 24675462
2012 Vitamin D receptor as a master regulator of the c-MYC/MXD1 network. Proceedings of the National Academy of Sciences of the United States of America 98 23112173
2014 A Bub1-Mad1 interaction targets the Mad1-Mad2 complex to unattached kinetochores to initiate the spindle checkpoint. The Journal of cell biology 97 24567362
1998 Repression by the Mad(Mxi1)-Sin3 complex. BioEssays : news and reviews in molecular, cellular and developmental biology 96 9819568
1995 Contrasting roles for Myc and Mad proteins in cellular growth and differentiation. Proceedings of the National Academy of Sciences of the United States of America 91 7667316
2012 Structure of human Mad1 C-terminal domain reveals its involvement in kinetochore targeting. Proceedings of the National Academy of Sciences of the United States of America 87 22493223
2011 Concise review: mesenchymal tumors: when stem cells go mad. Stem cells (Dayton, Ohio) 84 21425403
2014 MicroRNA-26b functions as a proapoptotic factor in porcine follicular Granulosa cells by targeting Sma-and Mad-related protein 4. Biology of reproduction 80 25395673
2001 The interplay between Mad and Myc in proliferation and differentiation. Trends in cell biology 80 11684436
2006 The Mad side of the Max network: antagonizing the function of Myc and more. Current topics in microbiology and immunology 72 16620026
1995 Repression of Myc-Ras cotransformation by Mad is mediated by multiple protein-protein interactions. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 67 7669717
2021 Characterization of SARS2 Nsp15 nuclease activity reveals it's mad about U. Nucleic acids research 66 34403466
1995 Differential effects by Mad and Max on transformation by cellular and viral oncoproteins. Oncogene 63 7630643
2020 Cyclin B1 scaffolds MAD1 at the kinetochore corona to activate the mitotic checkpoint. The EMBO journal 62 32202322
1933 STUDIES ON PSEUDORABIES (INFECTIOUS BULBAR PARALYSIS, MAD ITCH) : I. HISTOLOGY OF THE DISEASE, WITH A NOTE ON THE SYMPTOMATOLOGY. The Journal of experimental medicine 62 19870206
1999 Two MAD tails: what the recent knockouts of Mad1 and Mxi1 tell us about the MYC/MAX/MAD network. Biochimica et biophysica acta 59 10382539
2005 The roles of MAD1, MAD2 and MAD3 in meiotic progression and the segregation of nonexchange chromosomes. Nature genetics 58 15951820
2013 Spindle assembly checkpoint robustness requires Tpr-mediated regulation of Mad1/Mad2 proteostasis. The Journal of cell biology 57 24344181
2013 Mad, bad and dangerous to know: the biochemistry, ecology and evolution of slow loris venom. The journal of venomous animals and toxins including tropical diseases 55 24074353
1996 SIN3-dependent transcriptional repression by interaction with the Mad1 DNA-binding protein. Molecular and cellular biology 55 8754821
2002 Myc and Mad bHLHZ domains possess identical DNA-binding specificities but only partially overlapping functions in vivo. Proceedings of the National Academy of Sciences of the United States of America 52 12149476
2000 Analysis of Myc/Max/Mad network members in adipogenesis: inhibition of the proliferative burst and differentiation by ectopically expressed Mad1. Journal of cellular physiology 52 10797315
1994 The Max transcription factor network: involvement of Mad in differentiation and an approach to identification of target genes. Cold Spring Harbor symposia on quantitative biology 52 7587059
2012 The Mad1-Mad2 balancing act--a damaged spindle checkpoint in chromosome instability and cancer. Journal of cell science 51 23093575
2004 Localization of mitotic arrest deficient 1 (MAD1) in mouse oocytes during the first meiosis and its functions as a spindle checkpoint protein. Biology of reproduction 51 15342357
2003 Transcriptional regulation of mitotic checkpoint gene MAD1 by p53. The Journal of biological chemistry 51 12876282
2012 Functional interaction between the Arabidopsis orthologs of spindle assembly checkpoint proteins MAD1 and MAD2 and the nucleoporin NUA. Plant molecular biology 50 22457071
2003 Spindle checkpoint proteins Mad1 and Mad2 are required for cytostatic factor-mediated metaphase arrest. The Journal of cell biology 50 14691134
1999 Discrimination of solvent from protein regions in native Fouriers as a means of evaluating heavy-atom solutions in the MIR and MAD methods. Acta crystallographica. Section D, Biological crystallography 49 10089362
2009 Integration of BMP and Wnt signaling via vertebrate Smad1/5/8 and Drosophila Mad. Cytokine & growth factor reviews 48 19896409
2003 Mad dogs, Englishmen and apoptosis: the role of cell death in UV-induced skin cancer. Apoptosis : an international journal on programmed cell death 47 12815274
2000 Inhibition of proliferation and apoptosis by the transcriptional repressor Mad1. Repression of Fas-induced caspase-8 activation. The Journal of biological chemistry 46 10744730
2014 The Caenorhabditis elegans Myc-Mondo/Mad complexes integrate diverse longevity signals. PLoS genetics 45 24699255
2004 HAT cofactor Trrap regulates the mitotic checkpoint by modulation of Mad1 and Mad2 expression. The EMBO journal 44 15549134
2001 Gd-HPDO3A, a complex to obtain high-phasing-power heavy-atom derivatives for SAD and MAD experiments: results with tetragonal hen egg-white lysozyme. Acta crystallographica. Section D, Biological crystallography 44 11752774
2020 Cyclin B1-Cdk1 facilitates MAD1 release from the nuclear pore to ensure a robust spindle checkpoint. The Journal of cell biology 43 32236513
2000 Restricted patterning of vestigial expression in Drosophila wing imaginal discs requires synergistic activation by both Mad and the drifter POU domain transcription factor. Development (Cambridge, England) 42 10862753
1999 Phosphorylation of human MAD1 by the BUB1 kinase in vitro. Biochemical and biophysical research communications 42 10198256
1994 Assignment of the human MAD and MXI1 genes to chromosomes 2p12-p13 and 10q24-q25. Genomics 42 7829091
2007 Rb loss causes cancer by driving mitosis mad. Cancer cell 41 17222786
1998 The C. elegans MDL-1 and MXL-1 proteins can functionally substitute for vertebrate MAD and MAX. Oncogene 40 9764821
2020 Mitochondria-Associated Degradation Pathway (MAD) Function beyond the Outer Membrane. Cell reports 38 32668258
2011 MAD1 and its life as a MYC antagonist: an update. European journal of cell biology 37 21917351
2014 Endopolyploidization and flowering time are antagonistically regulated by checkpoint component MAD1 and immunity modulator MOS1. Nature communications 36 25429892
2023 Facilitating CG Simulations with MAD: The MArtini Database Server. Journal of chemical information and modeling 35 36656159
2020 An MXD1-derived repressor peptide identifies noncoding mediators of MYC-driven cell proliferation. Proceedings of the National Academy of Sciences of the United States of America 35 32156728
2015 Down regulation of miR-202 modulates Mxd1 and Sin3A repressor complexes to induce apoptosis of pancreatic cancer cells. Cancer biology & therapy 35 25611699
1997 MAD-related genes on 18q21.1, Smad2 and Smad4, are altered infrequently in esophageal squamous cell carcinoma. Japanese journal of cancer research : Gann 35 9197523
2009 Nemo kinase interacts with Mad to coordinate synaptic growth at the Drosophila neuromuscular junction. The Journal of cell biology 33 19451277
2011 Centromere-tethered Mps1 pombe homolog (Mph1) kinase is a sufficient marker for recruitment of the spindle checkpoint protein Bub1, but not Mad1. Proceedings of the National Academy of Sciences of the United States of America 32 22184248
1997 Analysis of the DNA-binding activities of Myc/Max/Mad network complexes during induced differentiation of U-937 monoblasts and F9 teratocarcinoma cells. Oncogene 32 9264414
2013 Brain tumor regulates neuromuscular synapse growth and endocytosis in Drosophila by suppressing mad expression. The Journal of neuroscience : the official journal of the Society for Neuroscience 31 23884941
2017 Direct interactions of mitotic arrest deficient 1 (MAD1) domains with each other and MAD2 conformers are required for mitotic checkpoint signaling. The Journal of biological chemistry 30 29162720
2011 Phosphorylation of Mad controls competition between wingless and BMP signaling. Science signaling 30 21990430
2021 Molecular mechanism of Mad1 kinetochore targeting by phosphorylated Bub1. EMBO reports 28 34013668
2011 Solution structure of the mSin3A PAH2-Pf1 SID1 complex: a Mad1/Mxd1-like interaction disrupted by MRG15 in the Rpd3S/Sin3S complex. Journal of molecular biology 28 21440557
2006 Structural aspects of interactions within the Myc/Max/Mad network. Current topics in microbiology and immunology 28 16620027
2016 Cep57 is a Mis12-interacting kinetochore protein involved in kinetochore targeting of Mad1-Mad2. Nature communications 27 26743940
2010 Kinetic analysis of the interaction of b/HLH/Z transcription factors Myc, Max, and Mad with cognate DNA. Biochemistry 27 20170194
2014 ATM-mediated Mad1 Serine 214 phosphorylation regulates Mad1 dimerization and the spindle assembly checkpoint. Carcinogenesis 26 24728176
2020 MAGI2-AS3 suppresses MYC signaling to inhibit cell proliferation and migration in ovarian cancer through targeting miR-525-5p/MXD1 axis. Cancer medicine 25 32681706
2019 ULK1 phosphorylates Mad1 to regulate spindle assembly checkpoint. Nucleic acids research 24 31291454
2018 MAD1: Kinetochore Receptors and Catalytic Mechanisms. Frontiers in cell and developmental biology 24 29868582
2014 A Golgi-localized pool of the mitotic checkpoint component Mad1 controls integrin secretion and cell migration. Current biology : CB 24 25447996
2013 Sma- and Mad-related protein 7 (Smad7) is required for embryonic eye development in the mouse. The Journal of biological chemistry 24 23426374
2022 Juxtaposition of Bub1 and Cdc20 on phosphorylated Mad1 during catalytic mitotic checkpoint complex assembly. Nature communications 23 36289199
2020 The MYCL and MXD1 transcription factors regulate the fitness of murine dendritic cells. Proceedings of the National Academy of Sciences of the United States of America 23 32071205
2017 Mxd1 mediates hypoxia-induced cisplatin resistance in osteosarcoma cells by repression of the PTEN tumor suppressor gene. Molecular carcinogenesis 23 28543796
2003 Dynamics of Myc/Max/Mad expression during luteinization of primate granulosa cells in vitro: association with periovulatory proliferation. Endocrinology 23 12639907
2000 Clinical implication of altered expression of Mad1 protein in human breast carcinoma. Cancer 23 10738221
2016 miR-382-5p Controls Hematopoietic Stem Cell Differentiation Through the Downregulation of MXD1. Stem cells and development 22 27520398