TY - JOUR
T1 - p53-independent apoptosis is induced by the p19ARF tumor suppressor
AU - Tsuji, Keitaro
AU - Mizumoto, Kiyohisa
AU - Sudo, Haruka
AU - Kouyama, Keisuke
AU - Ogata, Etsuro
AU - Matsuoka, Masaaki
PY - 2002/1/1
Y1 - 2002/1/1
N2 - p19ARF is a potent tumor suppressor. By inactivating Mdm2, p19ARF upregulates p53 activities to induce cell cycle arrest and sensitize cells to apoptosis in the presence of collateral signals. It has also been demonstrated that cell cycle arrest is induced by overexpressed p19ARF in p53-deficient mouse embryonic fibroblasts, only in the absence of the Mdm2 gene. Here, we show that apoptosis can be induced without additional apoptosis signals by expression of p19ARF using an adenovirus-mediated expression system in p53-intact cell lines as well as p53-deficient cell lines. Also, in primary mouse embryonic fibroblasts (MEFs) lacking p53/ARF, p53-independent apoptosis is induced irrespective of Mdm2 status by expression of p19ARF. In agreement, p19ARF-mediated apoptosis in U2OS cells, but not in Saos2 cells, was attenuated by coexpression of Mdm2. We thus conclude that there is a p53-independent pathway for p19ARF-induced apoptosis that is insensitive to inhibition by Mdm2.
AB - p19ARF is a potent tumor suppressor. By inactivating Mdm2, p19ARF upregulates p53 activities to induce cell cycle arrest and sensitize cells to apoptosis in the presence of collateral signals. It has also been demonstrated that cell cycle arrest is induced by overexpressed p19ARF in p53-deficient mouse embryonic fibroblasts, only in the absence of the Mdm2 gene. Here, we show that apoptosis can be induced without additional apoptosis signals by expression of p19ARF using an adenovirus-mediated expression system in p53-intact cell lines as well as p53-deficient cell lines. Also, in primary mouse embryonic fibroblasts (MEFs) lacking p53/ARF, p53-independent apoptosis is induced irrespective of Mdm2 status by expression of p19ARF. In agreement, p19ARF-mediated apoptosis in U2OS cells, but not in Saos2 cells, was attenuated by coexpression of Mdm2. We thus conclude that there is a p53-independent pathway for p19ARF-induced apoptosis that is insensitive to inhibition by Mdm2.
KW - Apoptosis
KW - Cell cycle arrest
KW - Mdm2
KW - p19
KW - p53
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UR - http://www.scopus.com/inward/citedby.url?scp=0036311122&partnerID=8YFLogxK
U2 - 10.1016/S0006-291X(02)00723-4
DO - 10.1016/S0006-291X(02)00723-4
M3 - Article
C2 - 12099684
AN - SCOPUS:0036311122
VL - 295
SP - 621
EP - 629
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -