Imperial College London


Faculty of MedicineNational Heart & Lung Institute

Chair in Cardiology



+44 (0)013 34621727m.d.schneider Website




ICTEM buildingHammersmith Campus






BibTex format

author = {Agah, R and Kirshenbaum, LA and Abdellatif, M and Truong, LD and Chakraborty, S and Michael, LH and Schneider, MD},
doi = {10.1172/JCI119817},
journal = {J Clin Invest},
pages = {2722--2728},
title = {Adenoviral delivery of E2F-1 directs cell cycle reentry and p53-independent apoptosis in postmitotic adult myocardium in vivo.},
url = {},
volume = {100},
year = {1997}

RIS format (EndNote, RefMan)

AB - Irreversible exit from the cell cycle precludes the ability of cardiac muscle cells to increase cell number after infarction. Using adenoviral E1A, we previously demonstrated dual pocket protein- and p300-dependent pathways in neonatal rat cardiac myocytes, and have proven that E2F-1, which occupies the Rb pocket, suffices for these actions of E1A. By contrast, the susceptibility of adult ventricular cells to viral delivery of exogenous cell cycle regulators has not been tested, in vitro or in vivo. In cultured adult ventricular myocytes, adenoviral gene transfer of E2F-1 induced expression of proliferating cell nuclear antigen, cyclin-dependent protein kinase 4, cell division cycle 2 kinase, DNA synthesis, and apoptosis. In vivo, adenoviral delivery of E2F-1 by direct injection into myocardium induced DNA synthesis, shown by 5'-bromodeoxyuridine incorporation, and accumulation in G2/M, by image analysis of Feulgen-stained nuclei. In p53(-)/- mice, the prevalence of G1 exit was more than twofold greater; however, E2F-1 evoked apoptosis and rapid mortality comparably in both backgrounds. Thus, the differential effects of E2F-1 on G1 exit in wild-type versus p53-deficient mice illustrate the combinatorial power of viral gene delivery to genetically defined recipients: E2F-1 can override the G1/S checkpoint in postmitotic ventricular myocytes in vitro and in vivo, but leads to apoptosis even in p53(-)/- mice.
AU - Agah,R
AU - Kirshenbaum,LA
AU - Abdellatif,M
AU - Truong,LD
AU - Chakraborty,S
AU - Michael,LH
AU - Schneider,MD
DO - 10.1172/JCI119817
EP - 2728
PY - 1997///
SN - 0021-9738
SP - 2722
TI - Adenoviral delivery of E2F-1 directs cell cycle reentry and p53-independent apoptosis in postmitotic adult myocardium in vivo.
T2 - J Clin Invest
UR -
UR -
VL - 100
ER -