The macromolecular state of the transcription factor E2F and glucocorticoid regulation of c-myc transcription

Kunsoo Rhee, Tianlin Ma, E. Aubrey Thompson

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Glucocorticoids inhibit transcription of the proto-oncogene c-myc in lymphoid cells of thymic origin. To determine if this effect is associated with changes in the properties of the transcription factor E2F, extracts were prepared from control and glucocorticoid-treated P1798 murine T lymphoma cells, and the macromolecular state of E2F was assessed by gel-mobility shift. Control extracts exhibit two predominant gel-mobility shift entities of which one corresponds to 'free' E2F. A second entity, complex C, has properties similar to those described for the complex containing E2F, p107, cyclin A, and Cdk2. Complex C disappears after addition of dexamethasone and is replaced by complex D. The mobility of this complex and its sensitivity to SV40 T antigen suggest that complex D corresponds to an E2F·p105(Rb-1) complex. Extracts from control and glucocorticoid-treated cells yield identical DNase I protection patterns on the c-myc P2 promoter. Furthermore, such extracts transcribe the c-myc P2 promoter in vitro with equal activity. The relative abundance of the E2F complexes was measured after addition of dexamethasone. Complex C disappears as cells withdraw from S phase, and complex D appears at this time. The genes encoding thymidine kinase (Tk-1) and p34(cdc2) (cdc2) are regulated with kinetics similar to those observed for changes in the macromolecular state of E2F. However, regulation of c-myc expression occurs long before any change in E2F. The macromolecular state of E2F may regulate expression of genes at the G1/S boundary. However, the data are not consistent with the hypothesis that association of E2F with tumor suppressor gene products such as p107 or p105(Rb-1) is relevant to glucocorticoid regulation of c-myc transcription.

Original languageEnglish (US)
Pages (from-to)17035-17042
Number of pages8
JournalJournal of Biological Chemistry
Volume269
Issue number25
StatePublished - Jun 24 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The macromolecular state of the transcription factor E2F and glucocorticoid regulation of c-myc transcription'. Together they form a unique fingerprint.

Cite this