spr-2, a suppressor of the egg-laying defect caused by loss of sel-12 presenilin in Caenorhabditis elegans, is a member of the SET protein subfamily.
Presenilin plays critical roles in the genesis of Alzheimer's disease and in LIN-12/Notch signaling during development. Here, we describe a screen for genes that influence presenilin level or activity in Caenorhabditis elegans. We identified four spr (suppressor of presenilin) genes by reverting the egg-laying defective phenotype caused by a null allele of the sel-12 presenilin gene. We analyzed the spr-2 gene in some detail. We show that loss of spr-2 activity suppresses the egg-laying defective phenotype of different sel-12 alleles and requires activity of the hop-1 presenilin gene, suggesting that suppression is accomplished by elevating presenilin activity rather than by bypassing the need for presenilin activity. We also show that SPR-2 is a nuclear protein and is a member of a protein subfamily that includes human SET, which has been identified in numerous different biochemical assays and at translocation breakpoints associated with a subtype of acute myeloid leukemia.
Wen
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Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA.
Levitan
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Li
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Greenwald
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D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D002467:Cell Nucleus / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D003001:Cloning, Molecular; D018509:DNA, Helminth; D004268:DNA-Binding Proteins; D005260:Female; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D015801:Helminth Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D056488:Histone Chaperones; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D010058:Oviposition / Q000502:physiology*; D010641:Phenotype; D011506:Proteins / Q000235:genetics; D014157:Transcription Factors
D029742:Caenorhabditis elegans Proteins; D002868:Chromosomal Proteins, Non-Histone; D018509:DNA, Helminth; D004268:DNA-Binding Proteins; D015801:Helminth Proteins; D056488:Histone Chaperones; C109040:Hop-1 protein, C elegans; D008164:Luminescent Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011506:Proteins; C095907:SEL-12 protein, C elegans; C513473:SET protein, human; C419776:Spr-2 protein, C elegans; D014157:Transcription Factors; D049452:Green Fluorescent Proteins