Abstract
v-Abl is an oncogenic form of the c-Abl nonreceptor tyrosine kinase. v-Abl induces transcription of c-myc, and c-Myc function is a necessary but not sufficient component of the v-Abl transformation program. Previously we showed that the E2F site in the c-myc promoter is a v-Abl response element and that v-Abl appears to induce c-myc by initiating a phosphorylation cascade that ultimately activates E2F-binding proteins. In this work we have investigated the signaling pathway between the v-Abl tyrosine kinase and activated E2F proteins. We show that the Ras GTPase and Raf1 serine/threonine kinase are required in this pathway. However, in contrast to other aspects of v-Abl signaling, induction of c-myc transcription is independent of the Rac GTPase. Our results also establish a requirement for activated cyclin-dependent kinases (cdks), as v-Abl-dependent induction of c-myc transcription is blocked by cdk inhibitor p21 and induction of c-myc is accompanied by activation of cdk2 and cdk4. Finally, we show that v-Abl-dependent induction of c-myc is accompanied by hyperphosphorylation of pRb, p107, and p130. On the basis of these data, we propose a model for the signaling path from v-Abl to c-myc.
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Dates
Type | When |
---|---|
Created | 18 years, 2 months ago (June 5, 2007, 5:15 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 14, 2021, 9:58 p.m.) |
Indexed | 1 year, 4 months ago (April 17, 2024, 6:30 a.m.) |
Issued | 28 years, 5 months ago (March 1, 1997) |
Published | 28 years, 5 months ago (March 1, 1997) |
Published Online | 28 years, 5 months ago (March 1, 1997) |
Published Print | 28 years, 5 months ago (March 1, 1997) |
@article{Zou_1997, title={Induction of c-myc transcription by the v-Abl tyrosine kinase requires Ras, Raf1, and cyclin-dependent kinases.}, volume={11}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.11.5.654}, DOI={10.1101/gad.11.5.654}, number={5}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Zou, X and Rudchenko, S and Wong, K and Calame, K}, year={1997}, month=mar, pages={654–662} }