44
B. Conradt
A
egl-l------1 ced-9------1 ced-4 -ced-3 - Cell Death
B
~ e ,!2
~ -~- ® - ~ -C'" D
I
Fig. 2A,B. Initiation of programmed cell death in C. elegans. A Genetically,
the egl-l gene initiates programmed cell death by negatively regulating ced-9.
B The EGL-l protein might initiate programmed cell death by binding to,
thereby regulating, the cell-death inhibitor protein CED-9 (see text for details)
support for the model that egl-l acts upstream of ced-9, ced-4, and ced-3
genetically (Conradt and Horvitz 1998).
The egl-l gene encodes a small protein with a domain that is reminiscent of the Bcl-2-homology region 3, called BH3 domain (Conradt and
Horvitz 1998). The EGL-l protein is therefore similar in structure to the
members of a rapidly growing subfamily of the family of Bcl-2-like
cell-death regulators, the BH3-only containing proteins, which include
the mammalian proteins Bad, Bid, Blk, HrklDP5, Bim, and NIP3 (reviewed by Adams and Cory 1998; Kelekar and Thompson 1997). The
BH3-only containing proteins were initially identified by virtue of their
binding to Bcl-2-like proteins. This binding depends on the BH3 domain of the BH3-only containing proteins which interacts with a hydrophobic cleft formed by the BH1, BH2, and BH3 domain of the Bcl-2like proteins. When overexpressed in mammalian cells, BH3-only
containing proteins can induce programmed cell death, and their ability
to do so appears to depend on their ability to bind to Bcl-2-like proteins.
However, the physiological role of these proteins in the programmed
cell-death process has not been established yet. The fact that egl-l acts
upstream of ced-9 genetically, suggests that at least some of the mammalian BH3-only containing proteins might similarly act as negative
regulators of Bcl-2-like cell-death inhibitors.
B. Conradt
A
egl-l------1 ced-9------1 ced-4 -ced-3 - Cell Death
B
~ e ,!2
~ -~- ® - ~ -C'" D
I
Fig. 2A,B. Initiation of programmed cell death in C. elegans. A Genetically,
the egl-l gene initiates programmed cell death by negatively regulating ced-9.
B The EGL-l protein might initiate programmed cell death by binding to,
thereby regulating, the cell-death inhibitor protein CED-9 (see text for details)
support for the model that egl-l acts upstream of ced-9, ced-4, and ced-3
genetically (Conradt and Horvitz 1998).
The egl-l gene encodes a small protein with a domain that is reminiscent of the Bcl-2-homology region 3, called BH3 domain (Conradt and
Horvitz 1998). The EGL-l protein is therefore similar in structure to the
members of a rapidly growing subfamily of the family of Bcl-2-like
cell-death regulators, the BH3-only containing proteins, which include
the mammalian proteins Bad, Bid, Blk, HrklDP5, Bim, and NIP3 (reviewed by Adams and Cory 1998; Kelekar and Thompson 1997). The
BH3-only containing proteins were initially identified by virtue of their
binding to Bcl-2-like proteins. This binding depends on the BH3 domain of the BH3-only containing proteins which interacts with a hydrophobic cleft formed by the BH1, BH2, and BH3 domain of the Bcl-2like proteins. When overexpressed in mammalian cells, BH3-only
containing proteins can induce programmed cell death, and their ability
to do so appears to depend on their ability to bind to Bcl-2-like proteins.
However, the physiological role of these proteins in the programmed
cell-death process has not been established yet. The fact that egl-l acts
upstream of ced-9 genetically, suggests that at least some of the mammalian BH3-only containing proteins might similarly act as negative
regulators of Bcl-2-like cell-death inhibitors.