Fas-Induced Caspase Denitrosylation
Joan B. Mannick,
1*
Alfred Hausladen,
2
Limin Liu,
3
Douglas
T. Hess,
2
Ming Zeng,
2
Qian X. Miao,
1
Laurie S. Kane,
2
Andrew J. Gow,
2
Jonathan S. Stamler
23*
Only a few intracellular S-nitrosylated proteins have been
identified, and it is unknown if protein
S-nitrosylation/denitrosylation is a component of signal transduction
cascades. Caspase-3 zymogens were found to be S-nitrosylated on their
catalytic-site cysteine in unstimulated human cell lines and
denitrosylated upon activation of the Fas apoptotic pathway. Decreased
caspase-3 S-nitrosylation was associated with an increase in
intracellular caspase activity. Fas therefore activates caspase-3 not
only by inducing the cleavage of the caspase zymogen to its active
subunits, but also by stimulating the denitrosylation of its
active-site thiol. Protein S-nitrosylation/denitrosylation can thus
serve as a regulatory process in signal transduction pathways.
1 Department of Adult Oncology, Dana Farber
Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
2 Department of Medicine, Divisions of Respiratory
and Cardiovascular Medicine and Department of Cell Biology, and
3 Howard Hughes Medical Institute, Duke University
Medical Center, Box 2612, 321 MSRB, Durham, NC 27710, USA.
*
To whom correspondence should be addressed. E-mail:
(J.S.S.) staml001{at}mc.duke.edu and (J.B.M.)
Joan_mannick{at}dfci.harvard.edu
