Involvement of BNIP1 in apoptosis and endoplasmic reticulum membrane fusion.
BNIP1, a member of the BH3-only protein family, was first discovered as one of the proteins that are capable of interacting with the antiapoptotic adenovirus E1B 19-kDa protein. Here we disclose a totally unexpected finding that BNIP1 is a component of the complex comprising syntaxin 18, an endoplasmic reticulum (ER)-located soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptor (SNARE). Functional analysis revealed that BNIP1 participates in the formation of the ER network structure, but not in membrane trafficking between the ER and Golgi. Notably, a highly conserved leucine residue in the BH3 domain of BNIP1 plays an important role not only in the induction of apoptosis but also in the binding of alpha-SNAP, an adaptor that serves as a link between the chaperone ATPase NSF and SNAREs. This predicts that alpha-SNAP may suppress apoptosis by competing with antiapoptotic proteins for the BH3 domain of BNIP1. Indeed, overexpression of alpha-SNAP markedly delayed staurosporine-induced apoptosis. Our results shed light on possible crosstalk between apparently independent cellular events, apoptosis and ER membrane fusion.
School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo, Japan.
Ken-ichi
K
Nakajima
Hidenori
H
Hirose
Mei
M
Taniguchi
Hirofumi
H
Kurashina
Kohei
K
Arasaki
Masami
M
Nagahama
Katsuko
K
Tani
Akitsugu
A
Yamamoto
Mitsuo
M
Tagaya
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism*; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050765:Qa-SNARE Proteins; D050766:Qb-SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry; D016415:Sequence Alignment; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D019311:Staurosporine / Q000494:pharmacology; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
C119020:BNIP1 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050765:Qa-SNARE Proteins; D050766:Qb-SNARE Proteins; C073173:SEC20 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D033921:Vesicular Transport Proteins; D019311:Staurosporine