Negative control of the helix-loop-helix family of myogenic regulators in the NFB mutant

Peterson, Charlotte A.; Gordon, Herman; Hall, Zach W.; Paterson, Bruce M.; Blau, Helen M.

doi:10.1016/0092-8674(90)90014-6

Cited by 68 publications

(39 citation statements)

References 70 publications

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“…The high level of MyoD expression by SKV-QECs in growth medium (Fig. 3a) is consistent with results obtained with other myoblasts (5,8,24). Expression of the other musclespecific mRNAs, including myogenin mRNA, in growth medium reflects the premature onset of terminal differentiation in a fraction of these cells as a result of local growth factor depletion; however, as previously shown (6), differentiation medium causes a strong induction of all of these mRNAs.…”

Section: Skv-qecssupporting

confidence: 80%

Transformation-defective v-ski induces MyoD and myogenin expression but not myotube formation.

1991

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The ski oncogene induces muscle differentiation in otherwise nonmyogenic quail embryo cells (C. Colmenares and E. Stavnezer, Cell 59:293-303, 1989). Here we report that v-ski induces both MyoD and myogenin expression, suggesting that activation of these muscle regulatory genes may be a critical step in ski-induced myogenesis. We also describe a transformation-defective mutant of v-ski (tdM5i) that fails to induce myotube formation, although it induces the expression of many muscle-specific genes, including the MyoD and myogenin genes. Therefore, if activation of MyoD and myogenin expression is a necessary component of the myogenic program triggered by ski, it is clearly insufficient to account for complete muscle differentiation.

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Section: Skv-qecssupporting

confidence: 80%

Transformation-defective v-ski induces MyoD and myogenin expression but not myotube formation.

1991

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“…2). This is not unusual because expression of MyoD has been previously found to be upregulated, maintained, or downregulated during terminal differentiation in different populations of C2 and CC,, myoblasts [14,33,34]. In our studies, we have not seen a decrease in c-&n expression until the cells were fully differentiated (Figs.…”

Section: Discussionsupporting

confidence: 43%

Expression of c‐jun/AP‐1 during myogenic differentiation in mouse C₂C₁₂ myoblasts

1993

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Mitogen withdrawal triggers myogenic differentiation in skeletal myoblasts in culture. We have examined the expression of the proto‐oncogene c‐jun during this process in mouse C2C12 myoblasts. c‐jun belongs to a family of immediate early genes whose expression is activated in cultured cells in response to the addition of serum growth factors. Interestingly, expression of c‐jun was maintained in mouse C2C12 and rat L6 myoblasts undergoing myogenic differentiation under low‐serum conditions. Previously it has been reported that expression of c‐jun is downregulated during differentiation of C2 cells. However, our results using C2C12 cells, a subclone of the C2 line, show that c‐jun mRNA, protein and the activator‐protein 1 (AP‐1) DNA‐binding activity were easily detected in proliferating myoblasts and differentiated myotubes. Although overexpression of c‐jun has been shown to block myogenic differentiation in C2 cells, results presented here suggest that expression of c‐jun at physiological levels may not interfere with skeletal myogenesis.

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“…The genetic locus that becomes mutated in the NFB line has not yet been defined, but levels of myogenic regulators were markedly reduced. The hypothesis, supported by heterokaryon fusion experiments, is that the mutation leads to production of a dominant repressor of myogenic regulators (55). A second nondifferentiating variant is WT-LT, a C2 line in which the expression of polyomavirus large T antigen blocks muscle cell differentiation (49,50).…”

Section: Resultsmentioning

confidence: 91%

“…The NFB cell line was selected for defective differentiation after mutagenesis of C2 cells. The NFB cell line fails to express myosin, a marker of differentiation, and does not exhibit fusion that leads to myotube formation (55). For the WT-LT cell line, differentiation is blocked by expression of the virus oncogene polyomavirus large T antigen.…”

Section: Methodsmentioning

confidence: 99%

Multiple Changes in E2F Function and Regulation Occur upon Muscle Differentiation

Shin

Paulding

et al. 1995

Molecular and Cellular Biology

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We have examined regulation of the E2F transcription factor during differentiation of muscle cells. E2F regulates many genes involved in growth control and is also the target of regulation by diverse cellular signals, including the RB family of growth suppressors (e.g., the retinoblastoma protein [RB], p107, and p130). The following aspects of E2F function and regulation during muscle differentiation were investigated: (i) proteinprotein interactions, (ii) protein levels, (iii) phosphorylation of the E2F protein, and (iv) transcriptional activity. A distinct E2F complex was present in differentiated cells but not in undifferentiated cells. The p130 protein was a prominent component of the E2F complex associated with differentiation. In contrast, in undifferentiated cells, the p107 protein was the prominent component in one of three E2F complexes. In addition, use of a differentiation-defective muscle line provided genetic and biochemical evidence that quiescence and differentiation are separable events. Exclusive formation of the E2F-p130 complex did not occur in this differentiation-defective line; however, E2F complexes diagnostic of quiescence were readily apparent. Thus, sole formation of the E2F-p130 complex is a necessary event in terminal differentiation. Other changes in E2F function and regulation upon differentiation include decreased phosphorylation and increased repression by E2F. These observations suggest that the regulation of E2F function during terminal differentiation may proceed through differential interaction within the RB family and/or phosphorylation.In many cells, the trigger event in differentiation is withdrawal from the cell cycle with subsequent distinct morphological transitions. Muscle cells are an excellent system for examining molecular mechanisms of differentiation because they exhibit both permanent cell cycle withdrawal and a distinctive phenotype. Differentiation involves a transition from myoblasts to myotubes. Myoblasts are undifferentiated cells and are characterized by rapidly growing, mononucleated cells. In contrast, differentiated cells, or myotubes, are multinucleated and tubular. Upon differentiation, myotubes also express several muscle-specific markers. Because differentiated muscle cells (myotubes) are permanently withdrawn from the cell cycle, cellular mechanisms for the initiation and maintenance of the differentiated state must also exist (5).Studies with viral oncogenes have indicated a critical role for the retinoblastoma family of growth suppressors (the retinoblastoma protein [RB], p107, and p130) in the differentiation pathway. The expression of E1A and polyomavirus large T antigen may block muscle differentiation (7,49,66). It is well established that these two divergent viral oncogenes can bind the RB family (69). Importantly, when the binding site for RB family members was mutated, both E1A and polyomavirus large T antigen mutants no longer blocked differentiation (7, 49). These studies suggest that RB family members function in the control of differenti...

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Negative control of the helix-loop-helix family of myogenic regulators in the NFB mutant

Cited by 68 publications

References 70 publications

Transformation-defective v-ski induces MyoD and myogenin expression but not myotube formation.

Transformation-defective v-ski induces MyoD and myogenin expression but not myotube formation.

Expression of c‐jun/AP‐1 during myogenic differentiation in mouse C₂C₁₂ myoblasts

Multiple Changes in E2F Function and Regulation Occur upon Muscle Differentiation

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Negative control of the helix-loop-helix family of myogenic regulators in the NFB mutant

Cited by 68 publications

References 70 publications

Transformation-defective v-ski induces MyoD and myogenin expression but not myotube formation.

Transformation-defective v-ski induces MyoD and myogenin expression but not myotube formation.

Expression of c‐jun/AP‐1 during myogenic differentiation in mouse C2C12 myoblasts

Multiple Changes in E2F Function and Regulation Occur upon Muscle Differentiation

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Expression of c‐jun/AP‐1 during myogenic differentiation in mouse C₂C₁₂ myoblasts