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Updated: Aug 13, 2026
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Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry
Published on: May 17, 2016
p57Kip2 is induced by MyoD through a p73-dependent pathway
Giovanna Vaccarello1, Rocco Figliola, Sabrina Cramerotti
1Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Università di Roma La Sapienza, Viale Regina Elena 324, 00161 Roma, Italy.
Journal of Molecular Biology
|January 13, 2006
Summary
Myogenic factor MyoD transcriptionally induces cyclin-dependent kinase inhibitor p57 via p73 family members. This process is E-box-independent and blocked by p21 in fibroblasts, suggesting chromatin-based repression.
Area of Science:
- Cell Biology
- Molecular Biology
- Muscle Development
Background:
- Cyclin-dependent kinase inhibitors p21 and p57 regulate skeletal muscle cell cycle arrest during differentiation.
- p57 is a target of the myogenic factor MyoD in cells lacking p21.
Purpose of the Study:
- To elucidate the mechanism by which MyoD induces p57 transcription.
- To identify the factors mediating p57 activation by MyoD.
- To investigate the role of p21 in regulating p57 induction.
Main Methods:
- Analysis of p57 transcriptional regulation by MyoD in fibroblasts and C2 myoblasts.
- Identification of transcription factors binding to the p57 promoter using a reporter construct.
- Overexpression of p73 isoforms and dominant-negative mutants.
- Assessment of p57 induction in the presence and absence of p21.
Main Results:
- MyoD induces p57 transcription via an E-box-independent mechanism requiring new protein synthesis.
- p73 family members (alpha, beta, delta) mediate MyoD-induced p57 activation through a 165bp promoter region.
- p73 isoform levels increase during muscle differentiation.
- p73-mediated p57 induction is blocked in p21-expressing cells, suggesting a cis-acting repressive mechanism, possibly involving chromatin structure.
Conclusions:
- MyoD activates p57 transcription through p73 family members in a p21-dependent manner.
- The presence of p21 prevents p73-mediated p57 induction, likely through chromatin remodeling.
- This study reveals a novel regulatory pathway for p57 in muscle differentiation.
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