Sequence analysis shows that Lifeguard belongs to a new evolutionarily conserved cytoprotective family.
Cellular sensitivity to apoptotic stimuli is determined by several regulatory proteins. The biological and biomedical impact of these regulatory proteins is of fundamental importance for understanding and controlling apoptotic processes. We used a bioinformatic approach to characterise the antiapoptotic protein Lifeguard (LFG). LFG is an evolutionarily well-conserved protein with homologues in many species. Due to its hydrophobic nature it is predicted to reside in cellular membranes, namely the endoplasmatic reticulum and the plasma membrane, with seven transmembrane spanners and a small cytoplasmic domain. The consensus motif of a protein family with unknown function UPF0005 was found in the C-terminus. The structure of Lifeguard resembles the antiapoptotic protein Bax Inhibitor-1 (BI-1). Concordantly, it was shown that Bax co-immunoprecipitates with LFG. Our results indicate that LFG belongs to a new cytoprotective family with evolutionarily conserved functions in the prevention of programmed cell death.
Reimers
Kerstin
K
Klinik für Plastische, Hand- und Wiederherstellungschirurgie, Medizinische Hochschule Hannover, D-30659 Hannover, Germany. reimers.kerstin@mh-hannover.de
Choi
Claudia Y-U
CY
Mau-Thek
Eddy
E
Vogt
Peter M
PM
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D017124:Conserved Sequence / Q000235:genetics*; D030561:Databases, Nucleic Acid; D019143:Evolution, Molecular; D015870:Gene Expression; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment / Q000379:methods; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; C400427:FAIM2 protein, human; D008565:Membrane Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein