1. Vitamin D3 Inhibits Wnt/β-Catenin and mTOR Signaling Pathways in Human Uterine Fibroid Cells.

    Journal of Clinical Endocrinology & Metabolism 101(4):1542 (2016) PMID 26820714 PMCID PMC4880168

    Vitamin D3 regulates Wnt/β-catenin and mTOR signaling pathways that are associated with cell proliferation and tumorigenicity, and thus vitamin D3 may have therapeutic utility as an effective, safe, long-term treatment option for human UFs.
  2. Transcriptional kinases: Less is more (or less).

    Nature Chemical Biology 12(1):4 (2016) PMID 26678610

  3. Somatic MED12 mutations in prostate cancer and uterine leiomyomas promote tumorigenesis through distinct mechanisms.

    Prostate 76(1):22 (2016) PMID 26383637

    Mediator is a multiprotein interface between eukaryotic gene-specific transcription factors and RNA polymerase II. Mutations in exon 2 of the gene encoding MED12, a key subunit of the regulatory kinase module in Mediator, are extremely frequent in uterine leiomyomas, breast fibroadenomas, and ph...
  4. Mediator subunit Med12 contributes to the maintenance of neural stem cell identity.

    BMC Developmental Biology 16(1):17 (2016) PMID 27188461 PMCID PMC4869265

    The RNA polymerase II transcriptional Mediator subunit Med12 is broadly implicated in vertebrate brain development, and genetic variation in human MED12 is associated with X-linked intellectual disability and neuropsychiatric disorders. Although prior studies have begun to elaborate the function...
  5. MED12 methylation by CARM1 sensitizes human breast cancer cells to chemotherapy drugs.

    Science advances 1(9):e1500463 (2015) PMID 26601288 PMCID PMC4646802

    The RNA polymerase II mediator complex subunit 12 (MED12) is frequently mutated in human cancers, and loss of MED12 has been shown to induce drug resistance through activation of transforming growth factor-β receptor (TGF-βR) signaling. We identified MED12 as a substrate for coactivator-associat...
  6. Mediator kinase module and human tumorigenesis.

    Critical Reviews in Biochemistry and Molecular ... 50(5):393 (2015) PMID 26182352 PMCID PMC4928375

    Mediator is a conserved multi-subunit signal processor through which regulatory informatiosn conveyed by gene-specific transcription factors is transduced to RNA Polymerase II (Pol II). In humans, MED13, MED12, CDK8 and Cyclin C (CycC) comprise a four-subunit "kinase" module that exists in varia...
  7. Mutations in Exon 1 highlight the role of MED12 in uterine leiomyomas.

    Human Mutation 35(9):1136 (2014) PMID 24980722

    Mediator regulates transcription by connecting gene-specific transcription factors to the RNA polymerase II initiation complex. We recently discovered by exome sequencing that specific exon 2 mutations in mediator complex subunit 12 (MED12) are extremely common in uterine leiomyomas. Subsequent ...
  8. Uterine leiomyoma-linked MED12 mutations disrupt mediator-associated CDK activity.

    Cell Reports 7(3):654 (2014) PMID 24746821 PMCID PMC4041330

    Somatic mutations in exon 2 of the RNA polymerase II transcriptional Mediator subunit MED12 occur at very high frequency (∼70%) in uterine leiomyomas. However, the influence of these mutations on Mediator function and the molecular basis for their tumorigenic potential remain unknown. To clarify...
  9. Mutations in MED12 cause X-linked Ohdo syndrome.

    The American Journal of Human Genetics 92(3):401 (2013) PMID 23395478 PMCID PMC3591845

    Ohdo syndrome comprises a heterogeneous group of disorders characterized by intellectual disability (ID) and typical facial features, including blepharophimosis. Clinically, these blepharophimosis-ID syndromes have been classified in five distinct subgroups, including the Maat-Kievit-Brunner (MK...
  10. MED12 mutations link intellectual disability syndromes with dysregulated GLI3-dependent Sonic Hedgehog signaling.

    PNAS 109(48):19763 (2012) PMID 23091001 PMCID PMC3511715

    Recurrent missense mutations in the RNA polymerase II Mediator subunit MED12 are associated with X-linked intellectual disability (XLID) and multiple congenital anomalies, including craniofacial, musculoskeletal, and behavioral defects in humans with FG (or Opitz-Kaveggia) and Lujan syndromes. H...
  11. Basic helix-loop-helix transcription factor Twist1 inhibits transactivator function of master chondrogenic regulator Sox9.

    Journal of Biological Chemistry 287(25):21082 (2012) PMID 22532563 PMCID PMC3375531

    Canonical Wnt signaling strongly inhibits chondrogenesis. Previously, we identified Twist1 as a critical downstream mediator of Wnt in repression of chondrocyte differentiation. However, the mechanistic basis for the antichondrogenic activity of Twist1 has not heretofore been established. Here, ...
  12. Lethal mitochondrial cardiomyopathy in a hypomorphic Med30 mouse mutant is ameliorated by ketogenic diet.

    PNAS 108(49):19678 (2011) PMID 22106289 PMCID PMC3241770

    Deficiencies of subunits of the transcriptional regulatory complex Mediator generally result in embryonic lethality, precluding study of its physiological function. Here we describe a missense mutation in Med30 causing progressive cardiomyopathy in homozygous mice that, although viable during la...
  13. Mediator and human disease.

    Seminars in Cell & Developmental Biology 22(7):776 (2011) PMID 21840410 PMCID PMC4100472

    Since the identification of a metazoan counterpart to yeast Mediator nearly 15 years ago, a convergent body of biochemical and molecular genetic studies have confirmed their structural and functional relationship as an integrative hub through which regulatory information conveyed by signal activ...
  14. Mediator is a transducer of amyloid-precursor-protein-dependent nuclear signalling.

    EMBO Reports 12(3):216 (2011) PMID 21293490 PMCID PMC3059912

    Regulated intramembrane proteolysis of the amyloid precursor-protein (APP) produces both a characterstic amyloid-β peptide that contributes to neuritic plaque formation and neurodegeneration in Alzheimer disease and a small APP intracellular domain (AICD) that transcriptionally activates genes i...
  15. DBC-1 mediates endocrine resistant breast cancer cell survival.

    Cell Cycle 9(6):1218 (2010) PMID 20237431

  16. MED19 and MED26 are synergistic functional targets of the RE1 silencing transcription factor in epigenetic silencing of neuronal gene expression.

    Journal of Biological Chemistry 284(5):2648 (2009) PMID 19049968 PMCID PMC2631966

    A key hub for the orchestration of epigenetic modifications necessary to restrict neuronal gene expression to the nervous system is the RE1 silencing transcription factor (REST; also known as neuron restrictive silencer factor, NRSF). REST suppresses the nonspecific and premature expression of n...
  17. Mediator links epigenetic silencing of neuronal gene expression with x-linked mental retardation.

    Molecular Cell 31(3):347 (2008) PMID 18691967 PMCID PMC2583939

    Mediator occupies a central role in RNA polymerase II transcription as a sensor, integrator, and processor of regulatory signals that converge on protein-coding gene promoters. Compared to its role in gene activation, little is known regarding the molecular mechanisms and biological implications...
  18. Mediator links epigenetic silencing of neuronal gene expression with x-linked mental retardation.

    Molecular Cell 31(3):347 (2008) PMID 18691967 PMCID PMC2583939

    Mediator occupies a central role in RNA polymerase II transcription as a sensor, integrator, and processor of regulatory signals that converge on protein-coding gene promoters. Compared to its role in gene activation, little is known regarding the molecular mechanisms and biological implications...
  19. Modulation of estrogen receptor alpha protein level and survival function by DBC-1.

    Molecular Endocrinology 21(7):1526 (2007) PMID 17473282

    Acquired resistance to endocrine therapy represents a major clinical obstacle to the successful management of estrogen-dependent breast cancers expressing estrogen receptor alpha (ERalpha). Because a switch from ligand-dependent to ligand-independent activation of ERalpha-regulated breast cancer...
  20. Mediator modulates Gli3-dependent Sonic hedgehog signaling.

    Molecular and Cellular Biology 26(23):8667 (2006) PMID 17000779 PMCID PMC1636813

    The physiological and pathological manifestations of Sonic hedgehog (Shh) signaling arise from the specification of unique transcriptional programs dependent upon key nuclear effectors of the Ci/Gli family of transcription factors. However, the underlying mechanism by which Gli proteins regulate...