The p53-inducible apoptotic protein AMID is not required for normal development and tumor suppression.
AMID is an apoptosis-inducing factor (AIF)-homologous and mitochondria-associated protein that has been implicated in caspase-independent apoptosis. Transcription of human AMID gene is upregulated by p53 and downregulated in tumors in comparison to their matched normal tissues, suggesting the possibility that AMID is involved in the downstream effects of p53. To investigate the physiological functions of AMID, we generated AMID-deficient mice by gene targeting. AMID-deficient mice are viable and fertile, develop normally and lack obvious phenotypic changes compared to wild-type mice up to 1 year old. AMID(-/-) mice up to 1 year old have no spontaneous tumors and show similar fibrosarcoma incidence after MCA inoculation compared to wild-type mice. AMID(-/-) embryonic fibroblasts exhibit normal proliferation but slightly increased resistance to genotoxin-induced growth arrest. These findings suggest that AMID is not required for normal development and p53-mediated tumor suppression.
Mei
J
J
National Jewish Medical and Research Center, Denver, CO, USA.
Webb
S
S
Zhang
B
B
Shu
H-B
HB
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D016147:Genes, Tumor Suppressor; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009152:Mutagenicity Tests; D009369:Neoplasms / Q000235:genetics; D012016:Reference Values; D017386:Sequence Homology, Amino Acid; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
C462504:ferroptosis suppressor protein 1, human; D051017:Apoptosis Regulatory Proteins; D024101:Mitochondrial Proteins; D016159:Tumor Suppressor Protein p53