TY - JOUR
T1 - c-FLIPR, a new regulator of death receptor-induced apoptosis
AU - Golks, Alexander
AU - Brenner, Dirk
AU - Fritsch, Cornelius
AU - Krammer, Peter H.
AU - Lavrik, Inna N.
PY - 2005/4/15
Y1 - 2005/4/15
N2 - c-FLIPs (c-FLICE inhibitory proteins) play an essential role in regulation of death receptor-induced apoptosis. Multiple splice variants of c-FLIP have been described on the mRNA level; so far only two of them, c-FLIPL and c-FLIPS, had been found to be expressed at the protein level. In this report, we reveal the endogenous expression of a third isoform of c-FLIP. We demonstrate its presence in a number of T and B cell lines as well as in primary human T cells. We identified this isoform as c-FLIPR, a death effector domain-only splice variant previously identified on the mRNA level. Importantly, c-FLIPR is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex upon CD95 stimulation. Several properties of c-FLIPR are similar to C-FLIPS: both isoforms have a short half-life, a similar pattern of expression during activation of primary human T cells, and are strongly induced in T cells upon CD3/CD28 costimulation. Taken together, our data demonstrate endogenous expression of c-FLIPR and similar roles of c-FLIPR and C-FLIPS isofonns in death receptor-mediated apoptosis.
AB - c-FLIPs (c-FLICE inhibitory proteins) play an essential role in regulation of death receptor-induced apoptosis. Multiple splice variants of c-FLIP have been described on the mRNA level; so far only two of them, c-FLIPL and c-FLIPS, had been found to be expressed at the protein level. In this report, we reveal the endogenous expression of a third isoform of c-FLIP. We demonstrate its presence in a number of T and B cell lines as well as in primary human T cells. We identified this isoform as c-FLIPR, a death effector domain-only splice variant previously identified on the mRNA level. Importantly, c-FLIPR is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex upon CD95 stimulation. Several properties of c-FLIPR are similar to C-FLIPS: both isoforms have a short half-life, a similar pattern of expression during activation of primary human T cells, and are strongly induced in T cells upon CD3/CD28 costimulation. Taken together, our data demonstrate endogenous expression of c-FLIPR and similar roles of c-FLIPR and C-FLIPS isofonns in death receptor-mediated apoptosis.
UR - http://www.scopus.com/inward/record.url?scp=17644378775&partnerID=8YFLogxK
U2 - 10.1074/jbc.M414425200
DO - 10.1074/jbc.M414425200
M3 - Article
C2 - 15701649
AN - SCOPUS:17644378775
SN - 0021-9258
VL - 280
SP - 14507
EP - 14513
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 15
ER -