Faculty Collaboration Database

E1A oncogene induction of cellular susceptibility to killing by cytolytic lymphocytes through target cell sensitization to apoptotic injury. Exp Cell Res 1999 Sep 15;251(2):414-23

Date

09/02/1999

Pubmed ID

10471326

DOI

10.1006/excr.1999.4597

Scopus ID

2-s2.0-0033568587   19 Citations

Abstract

E1A oncogene expression increases mammalian cell susceptibility to lysis by cytolytic lymphocytes (CLs) at a stage in this intercellular interaction that is independent of cell surface recognition events. Since CLs can induce either apoptotic or necrotic cell death, we asked whether E1A sensitization to injury-induced apoptosis is sufficient to explain E1A-induced cytolytic susceptibility. Mouse, rat, hamster, and human cells that were rendered cytolytic susceptible by E1A were also sensitized to CL-induced and chemically induced apoptosis. In contrast, E1A-positive cells were no more susceptible to injury-induced necrosis than E1A-negative cells. Similar to induction of cytolytic susceptibility and in contrast to other E1A activities, cellular sensitization to chemically induced apoptosis depended on high-level E1A oncoprotein expression. Loss of both cytolytic susceptibility and sensitization to chemically induced apoptosis was coselected during in vivo selection of E1A-positive sarcoma cells for increased tumorigenicity. Furthermore, E1A mutant proteins that cannot bind the cellular transcriptional coactivator, p300, and that fail to induce cytolytic susceptibility also failed to sensitize cells to injury-induced apoptosis. These data indicate that E1A induces susceptibility to killer cell-induced lysis through sensitization of cells to injury-induced apoptosis.

Author List

Cook JL, Routes BA, Walker TA, Colvin KL, Routes JM

MESH terms used to index this publication - Major topics in bold

3T3 Cells
Adenovirus E1A Proteins
Adenoviruses, Human
Animals
Anti-Bacterial Agents
Apoptosis
Cell Death
Cell Transformation, Viral
Cricetinae
Cytotoxicity, Immunologic
Depsipeptides
E1A-Associated p300 Protein
Humans
Killer Cells, Natural
Mice
Mutation
Necrosis
Nuclear Proteins
Peptides
Rats
Sarcoma, Experimental
Trans-Activators