Both the N-terminal fragment and the protein-protein interaction domain (PDZ domain) are required for the pro-apoptotic activity of presenilin-associated protein PSAP.
Presenilin-associated protein (PSAP) was originally identified as a PS1-associated, PDZ domain protein. In a subsequent study, PSAP was found to be a mitochondrial apoptotic molecule. In this study, we cloned the PSAP gene and found that it is composed of 12 exons and localizes on chromosome 6. To better understand the structure and function of PSAP, we have generated a series of antibodies that recognize different regions of PSAP. Using these antibodies, we found that PSAP is expressed in four isoforms as a result of differential splicing of exon 8 in addition to the use of either the first or the second ATG codon as the start codon. We also found that all these isoforms are localized in the mitochondria and are pro-apoptotic. Furthermore, our data revealed that the PDZ domain and N-terminal fragment are required for the pro-apoptotic activity of PSAP.
Mao
Guozhang
G
Department of Pathobiology, College of Veterinary Medicine, The University of Tennessee, 2407 River Dr., Knoxville, TN 37996, USA.
Tan
Jianxin
J
Gao
Wei
W
Shi
Yongchang
Y
Cui
Mei-Zhen
MZ
Xu
Xuemin
X
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D002918:Chymotrypsin / Q000378:metabolism; D018387:Codon, Initiator; D019286:Endopeptidase K / Q000378:metabolism; D005091:Exons; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007438:Introns; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D054731:PDZ Domains / Q000235:genetics*; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
D018387:Codon, Initiator; C402222:MTCH1 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020033:Protein Isoforms; D002918:Chymotrypsin; D014357:Trypsin; D019286:Endopeptidase K