Loss of spr-5 bypasses the requirement for the C.elegans presenilin sel-12 by derepressing hop-1

被引:41
作者
Eimer, S [1 ]
Lakowski, B [1 ]
Donhauser, R [1 ]
Baumeister, R [1 ]
机构
[1] Univ Munich, ABI, Dept Biochem, Mol Neurogenet Lab, D-80336 Munich, Germany
关键词
Alzheimer's disease; C; elegans; Notch; presenilins; suppressor genetics;
D O I
10.1093/emboj/cdf561
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Presenilins are part of a protease complex that is responsible for the intramembraneous cleavage of the amyloid precursor protein involved in Alzheimer's disease and of Notch receptors. In Caenorhabditis elegans, mutations in the presenilin sel-12 result in a highly penetrant egg-laying defect. spr-5 was identified as an extragenic suppressor of the sel-12 mutant phenotype. The SPR-5 protein has similarity to the human polyamine oxidase-like protein encoded by KIAA0601 that is part of the HDAC-CoREST co-repressor complex. Suppression of sel-12 by spr-5 requires the activity of HOP-1, the second somatic presenilin in C.elegans. spr-5 mutants derepress hop-1 expression 20- to 30-fold in the early larval stages when hop-1 normally is almost undetectable. SPR-1, a C.elegans homologue of CoREST, physically interacts with SPR-5. Moreover, down-regulation of SPR-1 by mutation or RNA interference also bypasses the need for sel-12. These data strongly suggest that SPR-5 and SPR-1 are part of a CoREST-like co-repressor complex in C.elegans. This complex might be recruited to the hop-1 locus controlling its expression during development.
引用
收藏
页码:5787 / 5796
页数:10
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