Regulation of muscle regulatory factors by DNA-binding, interacting proteins, and post-transcriptional modifications

Puri, Prem; Sartorelli, Vittorio

doi:10.1002/1097-4652(200011)185:2<155::aid-jcp1>3.0.co;2-z

Cited by 272 publications

(238 citation statements)

References 221 publications

(238 reference statements)

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“…Thr 115 is especially attractive since this site is phosphorylated by protein kinase C in response to FGF/FGFR signaling (Li et al, 1992). Although other phosphorylation sites have been reported, our data argue against those that induce MyoD degradation or enhance MyoD function (Puri and Sartorelli, 2000). Future studies should hopefully identify which FGFR(s) regulates this process.…”

Section: Discussionmentioning

confidence: 73%

“…Through its interaction with the E-proteins, and by cooperating with the MEF2 proteins, MyoD regulates muscle-specific gene expression. The activity of MyoD is controlled by post-translational mechanisms including protein-protein interaction, phosphorylation, acetylation and ubiquitination (Puri and Sartorelli, 2000). MyoD expression is regulated at the 258 bp core enhancer (Goldhamer et al, 1995) and distal regulatory region (Tapscott et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

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PAX-FKHR function as pangenes by simultaneously inducing and inhibiting myogenesis

et al. 2007

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Alveolar rhabdomyosarcomas (ARMS) escape terminal differentiation despite exhibiting a skeletal muscle phenotype. To understand the role of the ARMS-specific PAX-FKHR proteins in myogenesis, we characterized their regulation of MyoD expression and function. Reporter assays show that PAX-FKHR transactivate MyoD expression through its 258 bp core enhancer. Gel-shift assays confirm that PAX-FKHR bind to core enhancer sequences showing similarity to consensus PAX3/PAX-FKHRbinding sites. We show that while PAX3-FKHR activates the expression of endogenous MyoD and myogenin proteins in transduced NIH3T3 fibroblasts, it inhibits them from terminally differentiating as shown by low myogenin and myosin heavy chain expression, and lack of myotube formation. Attenuation of MyoD transcriptional activity via phosphorylation coupled to the lack of cell cycle arrest is the underlying mechanism for the differentiation block. Lastly, we show that fibroblast growth factor receptor signaling likely mediates the inhibition of differentiation by PAX3-FKHR. In a single experimental system we demonstrate that PAX3-FKHR can simultaneously induce myogenesis while preventing its completion. We propose 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.

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Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

PAX-FKHR function as pangenes by simultaneously inducing and inhibiting myogenesis

et al. 2007

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“…Id-1 is a dominant negative HLH protein that dimerizes preferentially to E proteins to prevent their interaction with MyoD or Myf5 (Norton et al, 1998). Similarly, M-twist represses myogenic differentiation by sequestering E proteins (Puri and Sartorelli, 2000). In addition, M-twist can directly block transcriptional activity of MyoD and MEF2 (Puri and Sartorelli, 2000) and compete with MyoD for binding to E-box sequences (Hebrok et al, 1997).…”

Section: Expression Of Muscle-related Genes During C2c12 Differentiationmentioning

confidence: 99%

“…Similarly, M-twist represses myogenic differentiation by sequestering E proteins (Puri and Sartorelli, 2000). In addition, M-twist can directly block transcriptional activity of MyoD and MEF2 (Puri and Sartorelli, 2000) and compete with MyoD for binding to E-box sequences (Hebrok et al, 1997). Therefore, our findings were consistent with patterns of gene expression that indicate C2C12 cell myogenesis.…”

Section: Expression Of Muscle-related Genes During C2c12 Differentiationmentioning

confidence: 99%

Genome‐wide examination of myoblast cell cycle withdrawal during differentiation

Shen

Collier

Hlaing

et al. 2002

Developmental Dynamics

107

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Skeletal and cardiac myocytes cease division within weeks of birth. Although skeletal muscle retains limited capacity for regeneration through recruitment of satellite cells, resident populations of adult myocardial stem cells have not been identified. Because cell cycle withdrawal accompanies myocyte differentiation, we hypothesized that C2C12 cells, a mouse myoblast cell line previously used to characterize myocyte differentiation, also would provide a model for studying cell cycle withdrawal during differentiation. C2C12 cells were differentiated in culture medium containing horse serum and harvested at various time points to characterize the expression profiles of known cell cycle and myogenic regulatory factors by immunoblot analysis. BrdU incorporation decreased dramatically in confluent cultures 48 hr after addition of horse serum, as cells started to form myotubes. This finding was preceded by up-regulation of MyoD, followed by myogenin, and activation of Bcl-2. Cyclin D1 was expressed in proliferating cultures and became undetectable in cultures containing 40% fused myotubes, as levels of p21 WAF1/Cip1 increased and ␣-actin became detectable. Because C2C12 myoblasts withdraw from the cell cycle during myocyte differentiation following a course that recapitulates this process in vivo, we performed a genome-wide screen to identify other gene products involved in this process. Using microarrays containing ϳ10,000 minimally redundant mouse sequences that map to the UniGene database of the National Center for Biotechnology Information, we compared gene expression profiles between proliferating, differentiating, and differentiated C2C12 cells and verified candidate genes demonstrating differential expression by RT-PCR. Cluster analysis of differentially expressed genes revealed groups of gene products involved in cell cycle withdrawal, muscle differentiation, and apoptosis. In addition, we identified several genes, including DDAH2 and Ly-6A, whose expression specifically was up-regulated during cell cycle withdrawal coincident with early myoblast differentiation. Developmental Dynamics 226:128 -138, 2003.

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“…At this stage, pRb is present in the active hypophosphorylated form, especially due to downregulation of cyclins A, E, and D1 and the upregulation of cdk inhibitors (Puri and Santorelli, 2000). It is possible that CDK9/CycT2 kinase activity is involved in the basal phosphorylation of the retinoblastoma protein and that pRb and CDK9/CycT2 cooperate to support MyoD-mediated myogenic transcription (Simone and Giordano, 2001).…”

Section: Cyclin T2 and Differentiationmentioning

confidence: 99%

Cyclin T: Three forms for different roles in physiological and pathological functions

Luca¹,

Falco

Baldi³

et al. 2002

Journal Cellular Physiology

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Cyclins are members of family of proteins involved in the cell cycle regulation. They are regulatory subunits of complexes with proteins called cyclin-dependent kinases (CDKs). There are three forms of cyclin T: cyclin T1, cyclin T2a, and T2b. All cyclin T contain an N-terminal ''cyclin homology box,'' the most conserved region among different members of the cyclin family that serves to bind CDK9. In addition to the N-terminal cyclin domain, cyclin T contains a putative coiled-coil motif, a His-rich motif, and a C-terminal PEST sequence. The CDK9/cyclin T complex is able to activate gene expression in a catalytic-dependent manner, phosphorylating the carboxy-terminal domain (CTD) of RNA polymerase II. In addition, only cyclin T1 supports interactions between Tat and TAR. The interaction of Tat with cyclin T1 alters the conformation of Tat to enhance the affinity and specificity of the Tat:TAR interaction. On the other hand, CDK9/cyclin T2 complexes are involved in the regulation of terminal differentiation in muscle cells.

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Regulation of muscle regulatory factors by DNA-binding, interacting proteins, and post-transcriptional modifications

Cited by 272 publications

References 221 publications

PAX-FKHR function as pangenes by simultaneously inducing and inhibiting myogenesis

PAX-FKHR function as pangenes by simultaneously inducing and inhibiting myogenesis

Genome‐wide examination of myoblast cell cycle withdrawal during differentiation

Cyclin T: Three forms for different roles in physiological and pathological functions

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