p57 super(K) super(i) super(p) super(2) is Induced by MyoD Through a p73-dependent Pathway
The cyclin-dependent-kinase inhibitors p21 and p57 are highly expressed in skeletal muscle where they redundantly control cell cycle arrest during differentiation. We have previously shown that p57 is a target of the myogenic factor MyoD in cells lacking p21. Here we show that MyoD induces p57 at th...
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| Published in: | Journal of molecular biology Vol. 356; no. 3; pp. 578 - 588 |
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| Main Authors: | , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
24-02-2006
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| Online Access: | Get full text |
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| Summary: | The cyclin-dependent-kinase inhibitors p21 and p57 are highly expressed in skeletal muscle where they redundantly control cell cycle arrest during differentiation. We have previously shown that p57 is a target of the myogenic factor MyoD in cells lacking p21. Here we show that MyoD induces p57 at the transcriptional level through a mechanism different from that involved in p21 regulation, since it is E-box-independent and requires new synthesized protein(s). We have identified p73 family members as the factors that mediate the activation of p57 through a 165bp promoter region. The levels of p73 alpha , beta and delta isoforms increase during muscle differentiation both in MyoD-expressing fibroblasts and in spontaneously differentiating C2 myoblasts. Moreover, the expression of a p73 dominant negative mutant interferes with the induction of p57. Finally, each of the isoforms up-regulated by MyoD, even when over-expressed alone, is capable of inducing p57 in p21-lacking fibroblasts. In contrast, the same p73 isoforms, either induced by MyoD or exogenously over-expressed, are unable to activate the expression of p57 in p21-expressing fibroblasts. Our finding that a transfected p57 promoter-reporter construct, unlike the endogenous gene, is responsive to both MyoD and p73 even in these cells, suggests that a cis-acting mechanism, probably involving a repressive chromatin structure, prevents the induction of p57 in p21-expressing fibroblasts. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-2 |
| ISSN: | 0022-2836 |
| DOI: | 10.1016/j.jmb.2005.12.024 |