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. 2000 Dec 19;97(26):14524-9.
doi: 10.1073/pnas.011446498.

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

C Wen  1 , D Levitan, X Li, I Greenwald
Affiliations

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

C Wen et al. Proc Natl Acad Sci U S A. .

Abstract

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.

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Figures

Figure 1
Figure 1
Alignment of SPR-2 and human SET. Identical amino acids are shaded. The SPR-2 sequence is based on our cDNA sequence analysis (see text). The positions of spr-2(ar211) Y206N, spr-2(ar214) E270stop, and spr-2(ar216) P203S are indicated by asterisks (*). The region used for construction of the tree shown in Fig. 2 ranges from K76 to V275 of SPR-2 (each marked with X).
Figure 2
Figure 2
The SET/Nap family. BLAST searches were done by using SPR-2, SET, and Nap1 as query sequences. To generate this tree, a region that seemed well conserved among all members of this family (as marked in Fig. 1) was used for CLUSTALW analysis. The two C. elegans SET/Nap proteins, SPR-2 and D2096.8, are encased within ovals, and the SET subfamily is boxed in gray. For clarity, we have in some cases renamed proteins, as various names are seen on the BLAST report because of the different synonyms for SET, and we have omitted sequences from other mammals, other species of Plasmodium, other plants, and relatively short expressed sequence tags. Accession numbers: SPR-2, AF321546; DmSET (Drosophila melanogaster), AE003708; MusSET (Mus musculus), AB015613; HsSET (Homo sapiens), Q01105; XenopusTAF-Ia (Xenopus laevis), AB022691; XenopusTFA-Ib, AB022692; TetraodonSET (Tetraodon fluviatilis), AF007219; MusTSPY, AF042180.1; Hs TSPY, U58096; HsTSPY-like, AAF03521.1; ArabidopsisSET2 (Arabidopsis thaliana), AC011765; ArabidopsisSET1, AC011809; PlasmodiumSET-like (Plasmodium falciparum), AJ238237; pombeNap-like2 (Schizosaccharomyces pombe), T40114; pombeNap-like, T41330; cerevisiaeNap1, NP 012974.1; CeD0296.8, T15896; AnisakisNap-like (Anisakis simplex), AJ237977; MusNap1–4, NP 032698.1; HsNap1–4 and MusNap1–1, NP 056596.1; HsNap1–1, NP 004528.1; HemicentrotusNap-like (Hemicentrotus pulcherrimus), D21877; MusNap1–2, NP 032697.1; HsNap1–2, BAA84706; HsNap1–3, NP 004529; and ArabidopsisNap-like, AAA50234.
Figure 3
Figure 3
Expression of SPR-2∷GFP. All L3 stage. (A) Nomarski photomicrograph. The π cells (23) are indicated with arrowheads. (B) GFP fluorescence in the nuclei of π cells of the same hermaphrodite shown in A. (C) GFP fluorescence in the nucleus of the anchor cell (marked with arrowhead) and other gonadal cells. (D) GFP fluorescence in intestinal nuclei.
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