Pax3 Inhibits Myogenic Differentiation of Cultured Myoblast Cells (*)

  title={Pax3 Inhibits Myogenic Differentiation of Cultured Myoblast Cells (*)},
  author={Jonathan A. Epstein and Paula Y. P. Lam and Lisa I. Jepeal and Richard L. Maas and David N. Shapiro},
  journal={The Journal of Biological Chemistry},
  pages={11719 - 11722}
Pax3 is an evolutionarily conserved transcription factor expressed in the lateral dermomyotome, a region that gives rise to limb muscle progenitors. Mutations in Pax-3 account for the mouse mutant Splotch which develops without limb musculature. We demonstrate that Pax3 can inhibit myogenic differentiation of C2C12 myoblasts normally induced by exposure to low serum. Specific missense mutations that affect the DNA binding characteristics of the two distinct DNA binding domains of Pax3 abolish… 
Pax3 induces differentiation of juvenile skeletal muscle stem cells without transcriptional upregulation of canonical myogenic regulatory factors
It is shown that constitutive expression of Pax3 in postnatal, juvenile mouse skeletal muscle stem cells, a subset of the heterogeneous satellite cell pool highly enriched for myogenic activity, potently induces differentiation.
Pax7 and myogenic progression in skeletal muscle satellite cells
It is shown that Pax7 is able to drive transcription in quiescent and activated satellite cells, and continues to do so in those cells that subsequently cease proliferation and withdraw from immediate differentiation, and may be involved in maintaining proliferation and preventing precocious differentiation.
PAX-FKHR function as pangenes by simultaneously inducing and inhibiting myogenesis
This work proposes a model whereby PAX-FKHR commit a yet undefined precursor cell to the myogenic lineage while at the same time inhibit terminal differentiation, thereby contributing to ARMS formation and fibroblast growth factor receptor signaling likely mediates the inhibition of differentiation.
Pax3 functions in cell survival and in pax7 regulation.
Examination of cell survival and gene expression in presomitic mesoderm, somites and neural tube of developing wild-type and Pax3 mutant (Splotch) mouse embryos establishes that Pax3 has complementary functions in MyoD activation and inhibition of apoptosis in the somitic mesderm and in repression of Pax7 during neural tube and somite development.
Mutation of Thr 115 in MyoD Positively Regulates Function in Murine Fibroblasts and Human Rhabdomyosarcoma Cells 1
Results suggest that Thr115 may play an important role in the regulation of MyoD function under conditions of high mitogenesis.
Integrated Functions of Pax3 and Pax7 in the Regulation of Proliferation, Cell Size and Myogenic Differentiation
In muscle progenitor cells, Pax3 and Pax7 function to maintain expression of myogenic regulatory factors, and promote population expansion, but are also required for myogenic differentiation to proceed.
cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene.
Alveolar rhabdomyosarcoma is an aggressive pediatric cancer of striated muscle characterized in 60% of cases by a t(2;13)(q35;q14). This results in the fusion of PAX3, a developmental transcription
AKT and PAX3-FKHR cooperation enforces myogenic differentiation blockade in alveolar rhabdomyosarcoma cell
It is reported that AKT acts, in part, by modulating PAX3-FKHR transcriptional activity via phosphorylation in the maintenance of the myogenic differentiation blockade in established mouse models of ARMS cells, causing a failure in differentiation.
Mutation of Thr115 in MyoD positively regulates function in murine fibroblasts and human rhabdomyosarcoma cells.
  • L. N. Liu, P. Dias, P. Houghton
  • Biology
    Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
  • 1998
A mutant MyoD with a single amino acid substitution that disrupts the PKC phosphorylation site (Thr115) within the conserved basic domain suggests that Thr115 may play an important role in the regulation of Myo D function under conditions of high mitogenic conditions.


Molecular cloning and characterization of a human PAX-7 cDNA expressed in normal and neoplastic myocytes.
Analysis of the DNA-binding properties of the Pax-7 paired domain revealed that it binds DNA in a sequence-specific manner indistinguishable from that of the paralogous Pax-3 protein, suggesting that overexpression of these PAX genes may be involved in the genesis of myogenic tumors.
A novel human muscle factor related to but distinct from MyoD1 induces myogenic conversion in 10T1/2 fibroblasts.
Nucleotide sequence analysis and the identification of the corresponding gene indicate that human Myf‐5 is a member of a small gene family which also contains the human homologue to MyoD1, a different protein which nevertheless is capable of inducing the myogenic phenotype in embryonic C3H mouse 10T1/2 ‘fibroblasts’.
Myogenin gene disruption results in perinatal lethality because of severe muscle defect
Evidence that myogenin is crucial for muscle development in utero is shown and it is demonstrated that other members of the myogenic gene family cannot compensate for the defect.
A gene with homology to the myc similarity region of MyoD1 is expressed during myogenesis and is sufficient to activate the muscle differentiation program.
The existence of a family of myogenic regulatory genes that share a conserved motif with c-myc is suggested, which is sufficient to activate the muscle differentiation program and may substitute for MyoD1 in certain developmental situations.
bHLH factors in muscle development: dead lines and commitments, what to leave in and what to leave out.
The models that emerged from studies of the myogenic factors in tissue culture are reviewed and the potential functions of these factors in the embryo are reconsidered in light of recent gene-targeting experiments.
Fusion of PAX3 to a member of the forkhead family of transcription factors in human alveolar rhabdomyosarcoma.
Formation of chimeric transcription factors has now been implicated in diverse human tumors of myogenic, hematopoietic, neuroectodermal, and adipocytic origin, suggesting that transcriptional deregulation is a common mechanism of tumorigenesis.
Pax‐3, a novel murine DNA binding protein expressed during early neurogenesis.
The isolation and characterization of Pax‐3 is described, a novel murine paired box gene expressed exclusively during embryogenesis that specifically recognizes the e5 sequence present upstream of the Drosophila even‐skipped gene.
Molecular basis of splotch and Waardenburg Pax-3 mutations.
Pax-3 mutations found in splotch alleles and WS1 individuals change DNA binding and, in the case of a protein product of the Sp allele, dimerization, which defines the molecular nature of the mutants.