POST-TRANSLATIONAL MODIFICATIONS ON E2F1 FOLLOWING DNA DAMAGE REGULATE pRB AND E2F1 INTERACTIONS
Year: 2009
Type: dissertation
Abstract: Cancer development involves the loss of the pRB tumor suppressor and activation of E2F-dependent transcription. Cell proliferation and apoptosis are both controlled by the E2F1 transcription factor, where it acts as either an oncogene or a tumor suppressor gene. While the oncogenic activity of E2F1 is known to be controlled through its direct interaction with pRB, its tumor suppressor role remains uncharacterized. In this thesis, the role of E2F1 as a tumor suppressor was studied by investigating how the DNA damage response interferes with E2Fl-pRB interactions, thus inducing apoptosis. Following DNA damage, E2F1 is stabilized by phosphorylation of serine residues through ATM and Chk2, and acetylation of lysine residues through P/CAF. I demonstrated that serine 31 phosophorylation and acetylation of multiple lysines on E2F1 disrupt the pRB-E2Fl interaction thus allowing E2F1 to induce apoptosis. Furthermore, phosphorylation and acetylation events occur independently of one another.
Author: Palander, Olivia
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7023948695