A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity.
Bcl-2 and Bcl-XL serve as critical inhibitors of apoptosis triggered by a broad range of stimuli, mainly acting on the mitochondria. We identified two members of the reticulon (RTN) family as Bcl-XL binding proteins, i.e., NSP-C (RTN1-C) and a new family member, RTN-XS, both of which did not belong to the Bcl-2 family and were predominantly localized on the endoplasmic reticulum (ER). RTN-XS interacted with both Bcl-XL and Bcl-2, increased the localization of Bcl-XL and Bcl-2 on the ER, and reduced the anti-apoptotic activity of Bcl-XL and Bcl-2. On the other hand, NSP-C interacted only with Bcl-XL, affected the localization of Bcl-XL, and reduced Bcl-XL activity, but had no effect on Bcl-2. These results suggest that RTN family proteins can modulate the anti-apoptotic activity of Bcl-XL and Bcl-2 by binding with them and can change their localization to the ER.
Tagami
S
S
Department of Medical Genetics, Biomedical Research Center, Osaka University Graduate School of Medicine, Suita, Japan.
Eguchi
Y
Y
Kinoshita
M
M
Takeda
M
M
Tsujimoto
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019556:COS Cells / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D018076:DNA, Complementary / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells / Q000378:metabolism; D008565:Membrane Proteins; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000070798:Nogo Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000378:metabolism; D014178:Translocation, Genetic; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D002352:Carrier Proteins; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C081781:RTN1 protein, human; C000603199:RTN4 protein, human; D051020:bcl-X Protein