A Protein Synthesis-Dependent Increase in E2F1 mRNA Correlates with Growth Regulation of the Dihydrofolate Reductase Promoter

• DOI: 10.1128/mcb.13.3.1610-1618.1993
• Publication Date: 2021-06-06T08:19:09Z
• Authors: Jill E. Slansky; Yue Li; William G. Kaelin; Peggy J. Farnham
• Keywords: Dihydrofolate reductase; E2F; E2F1; Transcription; Response element

Enhanced expression of genes involved in nucleotide biosynthesis, such as dihydrofolate reductase (DHFR), is a hallmark entrance into the DNA synthesis (S) phase mammalian cell cycle. To investigate regulated DHFR gene, we stimulated serum-starved NIH 3T3 cells to synchronously reenter Our previous results show that cis-acting element at site transcription initiation necessary for serum regulation. Recently, this has been demonstrated bind cloned factor E2F. In study, focused on role E2F growth regulation DHFR. We single site, absence or presence other promoter elements, was sufficient growth-regulated activity. Next, showed increase mRNA G1/S-phase boundary required protein synthesis, raising possibility protein(s) lacking transcription. found that, similar expression, levels murine E2F1 were low and increased synthesis-dependent manner. Furthermore, cotransfection experiment, human 22-fold cells. suggest may be key absent Expression also abolished serum-stimulated resulted patterns those seen with adenoviral oncoprotein E1A. summary, provide evidence importance alterations have severe consequences control cellular proliferation.