Crosstalk between E2F3 and p19ARF/p53 in the regulation of cell cycle progression and tumorigenesis

E2F activity was originally identified as a critical component of the cellular machinery responsible for promoting cell cycle progression that is co-opted during transformation and tumorigenesis. Classic E2F target genes have functions required for S-phase entry and progression. However, the role of E2F has expanded in recent years through the identification of novel E2F target genes. Now E2F is linked to many different cellular processes beyond basic cell cycle control. One such example is p19ARF, a positive upstream regulator of the p53 tumor suppressor protein. This dissertation examines the relationship between one member of the E2F family of transcription factors, E2F3, and the p19ARF/p53 pathway. E2F3 has previously been shown to be critical for cell cycle re-entry, cellular proliferation, and tumor development. The contribution of p19ARF/p53 to E2F3 function was assessed through the generation of compound mutant cells and mice. The nature of the relationship between E2F3, p19ARF, and p53 was highly context dependent. E2F3 is required to repress pl9Arf expression in quiescent cells. This places E2F3 upstream of p19ARF and p53 during cell cycle re-entry.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Aslanian, Aaron Spencer

Advisor dc:contributor.advisor

• Jacqueline A. Lees.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/33755

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/33755