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554 Cell Death (Apoptosis)

at least some apoptotic cells. Thus, although various fac- ACKNOWLEDGMENT
tors participating in phagocytosis have been identified, it
will be necessary to find further components involved in I thank all members of Dr. Nagata’s laboratory in Osaka Bioscience
this process to understand the molecular mechanism of Institute and Osaka University Medical School for helping during my
clearance of apoptotic cells in our bodies. initial works. I am grateful to Drs. S. Nagata and H. Sakahira in Osaka
University Medical School for helpful comments on the manuscript and
to Dr. C. Weissmann at the Imperial College School of Medicine for
supports, discussion, and encouragement.
IX. PERSPECTIVES

Not only cell growth and differentiation factors but also SEE ALSO THE FOLLOWING ARTICLES
death factors regulate homeostasis of organisms. The
death factors activate a caspase cascade through their spe-
CHROMATIN STRUCTURE AND MODIFICATION • GENE
cific receptors. Although it is said that procaspase-8 is self-
EXPRESSION,REGULATION OF • IMMUNOLOGY-AUTO-
cleaved simply following activation by oligomerization,
IMMUNITY • MAMMALIAN CELL CULTURE • RIBOZYMES
the precise mechanism is still unclear. Some unknown
• TRANSLATION OF RNA TO PROTEIN
additional factor(s) may be required for this process to
generate active caspase-8 more efficiently and remain to
be identified by future analyses. Furthermore, it is known
that there is caspase-independent apoptosis. It would be BIBLIOGRAPHY
important to investigate what kinds of factors are involved
in such apoptotic pathways. The mechanism of apoptotic Budihardjo, I., Oliver, H., Lutter, M., Luo, X., and Wang, X. (1999).
“Biochemical pathways of caspase activation during apoptosis,” Annu.
DNAfragmentationhasbeenlargelyclarifiedbybiochem-
Rev. Cell Dev. Biol. 15, 269–290.
ical approaches, but the mitochondrial pathway for death
Bratton, S. B., MacFarlane, M., Cain, K., and Cohen, G. M. (2000).
signals remains elusive. How are apoptotic signals trans- “Proteincomplexesactivatedistinctcaspasecascadesindeathreceptor
duced in mitochondria? Which factors participate in mi- and stress-induced apoptosis,” Exp. Cell Res. 256, 27–33.
tochondrial apoptosis? Cell-free systems using isolated Ferri, K. F., and Kroemer, G. (2000). “Control of apoptotic DNA degra-
mitochondria may lead to a satisfactory solution of these dation,” Nat. Cell Biol. 2, E63-4.
Green, D. R., and Reed, J. C. (1998). “Mitochondria and apoptosis,”
problems.
Science 281, 1309–1312.
Cell death occurs without cell-autonomous DNA degra- Liu, Q. A., and Hengartner, M. O. (1999). “The molecular mechanism
dation in cells devoid of CAD activity and developmental of programmed cell death in C,” Elegans. Ann. N. Y. Acad. Sci. 887,
processes appear to be normal (without drastic changes) 92–104.
despite the lack of functional CAD. Why has a compli- Nagata, S. (1997). “Apoptosis by death factor,” Cell 88, 355–365.
Nagata, S. (2000). “Steering anti-cancer drugs away from the TRAIL,”
cated CAD/ICAD system evolved in our bodies? One pos-
Nat. Med. 6, 502–503.
sibility is that this system precludes the transformation of Nagata, S. (2000). “Apoptotic DNA fragmentation,” Exp. Cell Res. 256,
phagocytes by dangerous genes such as oncogenes or vi- 12–18.
ral genes. Another possibility is that the cell-autonomous Raff, M. (1998). “Cell suicide for beginners,” Nature 396, 119–122.
Stroh, C., and Schulze-Osthoff, K. (1998). “Death by a thousand cuts:
DNA fragmentation mechanism reduces autoimmune re-
An ever-increasing list of caspase substrates,” Cell Death Diff. 5, 997–
sponses against nucleosomal DNA, which is known as
1000.
a strong autoantigen. Nucleosomal DNA released from Thornberry, N. A., and Lazebnik, Y. (1998). “Caspases: Enemies within,”
apoptotic cells during developmental processes could lead Science 281, 1312–1316.
to autoimmunity. Alternatively, the CAD/ICAD system Yeh, W. C., Hakem, R., Woo, M., and Mak, T. W. (1999). “Gene targeting
in the analysis of mammalian apoptosis and TNF receptor superfamily
may promote the recycling of the DNA components. Anal-
signaling,” Immunol. Rev. 169, 283–302.
yses of CAD/ICAD system-deficient mice may cast light
Wyllie, A. H., Kerr, J. F. R., and Currie, A. R. (1980). “Cell death: The
on these questions. Furthermore, the number of genes rec- significance of apoptosis,” Int. Rev. Cytol. 68, 251–306.
ognized as being involved in phagocytosis of apoptotic Wyllie, A. H. (1980). “Glucocorticoid-induced thymocyte apoptosis is
cells is gradually increasing due to genetic and molecu- associated with endogenous endonuclease activation,” Nature 284,
lar biological analyses. Thus, the understanding of detail 555–556.
Zhang, J., Liu, X., Scherer, D. C., van Kaer, L., Wang, X., and Xu, M.
molecular mechanisms of apoptosis deepens as science is
(1998). “Resistance to DNA fragmentation and chromatin condensa-
progressed, so the elucidation of overall mechanisms for tion in mice lacking the DNA fragmentation factor 45,” Proc. Natl.
apoptosis through death receptors may not be so far off. Acad. Sci. U.S.A. 95, 12480–12485.