title: A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia.
abstract: We report the first identified mutation in the gene encoding human cytochrome c (CYCS). Glycine 41, invariant throughout eukaryotes, is substituted by serine in a family with autosomal dominant thrombocytopenia caused by dysregulated platelet formation. The mutation yields a cytochrome c variant with enhanced apoptotic activity in vitro. Notably, the family has no other phenotypic indication of abnormal apoptosis, implying that cytochrome c activity is not a critical regulator of most physiological apoptosis.
authors.affiliation: Department of Biochemistry, University of Otago, PO Box 56, Dunedin 9054, New Zealand. ian.morison@otago.ac.nz
authors.forename: Ian M
authors.initials: IM
authors.lastname: Morison
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Cramer Bordé
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Cheesman
authors.forename: Pak Leng
authors.initials: PL
authors.lastname: Cheong
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Holyoake
authors.forename: Serge
authors.initials: S
authors.lastname: Fichelson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Weeks
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lo
authors.forename: Stefan M K
authors.initials: SM
authors.lastname: Davies
authors.forename: Sigurd M
authors.initials: SM
authors.lastname: Wilbanks
authors.forename: Robert D
authors.initials: RD
authors.lastname: Fagerlund
authors.forename: Mathew W
authors.initials: MW
authors.lastname: Ludgate
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: da Silva Tatley
authors.forename: Melanie S A
authors.initials: MS
authors.lastname: Coker
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Bockett
authors.forename: Gillian
authors.initials: G
authors.lastname: Hughes
authors.forename: Diana A
authors.initials: DA
authors.lastname: Pippig
authors.forename: Mark P
authors.initials: MP
authors.lastname: Smith
authors.forename: Claude
authors.initials: C
authors.lastname: Capron
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Ledgerwood
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D053477:Apoptotic Protease-Activating Factor 1 / Q000378:metabolism; D045304:Cytochromes c / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D010084:Oxidation-Reduction; D010375:Pedigree; D010976:Platelet Count; D012694:Serine / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction; D013921:Thrombocytopenia / Q000209:etiology* / Q000473:pathology
chemical_list: C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D012694:Serine; D045304:Cytochromes c