A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia.
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.
Morison
Ian M
IM
Department of Biochemistry, University of Otago, PO Box 56, Dunedin 9054, New Zealand. ian.morison@otago.ac.nz
Cramer Bordé
Elisabeth M
EM
Cheesman
Emma J
EJ
Cheong
Pak Leng
PL
Holyoake
Andrew J
AJ
Fichelson
Serge
S
Weeks
Robert J
RJ
Lo
Alexandra
A
Davies
Stefan M K
SM
Wilbanks
Sigurd M
SM
Fagerlund
Robert D
RD
Ludgate
Mathew W
MW
da Silva Tatley
Fernanda M
FM
Coker
Melanie S A
MS
Bockett
Nicholas A
NA
Hughes
Gillian
G
Pippig
Diana A
DA
Smith
Mark P
MP
Capron
Claude
C
Ledgerwood
Elizabeth C
EC
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
C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D012694:Serine; D045304:Cytochromes c