Bcl-2 inhibits p53 nuclear import following DNA damage.
Bcl-2 is an integral membrane oncoprotein that localizes to membranes of the mitochondria, endoplasmic reticulum, and nuclear envelope. Bcl-2 is a member of a family of cell death regulators and functions to inhibit apoptosis. Using confocal microscopy and immunoblotting we show that the ability of bcl-2 to suppress cell death following genotoxic damage can be a consequence of inhibiting nuclear import of induced wild-type p53 protein. Our data suggests that the ability of bcl-2 to modulate trafficking events is not cell type specific. These data support a 'gatekeeper' mechanism for cell death suppression by bcl-2.
Beham
A
A
Department of Molecular Pathology, University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
Marin
M C
MC
Fernandez
A
A
Herrmann
J
J
Brisbay
S
S
Tari
A M
AM
Lopez-Berestein
G
G
Lozano
G
G
Sarkiss
M
M
McDonnell
T J
TJ
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D001692:Biological Transport / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism*; D003110:Colonic Neoplasms; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D011471:Prostatic Neoplasms; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors*
D019253:Proto-Oncogene Proteins c-bcl-2; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53