Gene Ther Mol Biol Vol 2, 103-117. August 7, 1998.
EGR-1 prevents growth arrest by induction of c-myc Scott A. Crist1,2, Sumathi Krishnan1, Seong-Su Han1, Aysegul Nalca1,2, and Vivek M. Rangnekar1,2,3,4,* 1
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Department of Surgery, Division of Urology ; Department of Microbiology and Immunology ; Graduate
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Center for Toxicology ; and Markey Cancer Center ; University of Kentucky, Lexington, KY 40536. ______________________________________________________________________________________ ________________ * Correspondence: Vivek M. Rangnekar Combs Research Building, Room 303, University of Kentucky, 800 Rose Street, Lexington, KY 40536; Tel. (606) 257-2677; Fax. (606) 257-9608; E-mail: vmrang01@pop.uky.edu
Summary The zinc-finger transcription factor EGR-1 provides protection from G1 phase growth arrest. We present here evidence that this protective effect of EGR-1 is linked to upregulation of c-myc RNA and protein by induction of the c-myc promoter. Growth arrest involves c-myc downregulation and hypophosphorylation of the retinoblastoma susceptibility protein RB, but upregulation of c-myc prevents hypophosphorylation of RB and provides protection from growth arrest. These findings suggest a downstream mechanism for EGR-1 function as an inhibitor of G1 phase growth arrest. Because Egr-1 and c-myc are involved in determining cell fate in response to diverse exogenous signals, the findings of the present study can be extended to model systems for proliferation, cellular differentiation, and programmed cell death.