SPK-1, an SR protein kinase, inhibits programmed cell death in Caenorhabditis elegans.
To identify genes involved in protecting cells from programmed cell death in Caenorhabditis elegans, we performed a genetic screen to isolate mutations that cause an increase in the number of programmed cell deaths. We screened for suppressors of the cell-death defect caused by a partial loss-of-function mutation in ced-4, which encodes an Apaf-1 homolog that promotes programmed cell death by activating the caspase CED-3. We identified one extragenic ced-4 suppressor, which has a mutation in the gene spk-1. The spk-1 gene encodes a protein homologous to serine-arginine-rich (SR) protein kinases, which are thought to regulate splicing. Previous work suggests that ced-4 can be alternatively spliced and that the splice variants function oppositely, with the longer transcript (ced-4L) inhibiting programmed cell death. spk-1 might promote cell survival by increasing the amount of the protective ced-4L splice variant. We conclude that programmed cell death in C. elegans is regulated by an alternative splicing event controlled by the SR protein kinase SPK-1.
Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Brendan D
BD
Galvin
Daniel P
DP
Denning
H Robert
HR
Horvitz
D000483:Alleles; D017398:Alternative Splicing; D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics; D017238:Genes, Helminth; D008957:Models, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013489:Suppression, Genetic
D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; C089224:Ced-4 protein, C elegans; C574427:SPK-1 protein, C elegans; D017346:Protein Serine-Threonine Kinases
Cell Death Differ. 2008 Dec;15(12):1815-23
18806759
Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9155-60
9689050
Cell. 1993 Aug 27;74(4):597-608
8358789
Nature. 1992 Apr 9;356(6369):494-9
1560823
Nature. 1994 May 26;369(6478):318-20
7910376
Genetics. 1974 May;77(1):71-94
4366476
Development. 2003 Sep;130(17):4057-71
12874127
Nature. 2000 Oct 12;407(6805):796-801
11048731
Development. 1992 Oct;116(2):309-20
1286611
Development. 1991 Jun;112(2):591-603
1794327
Dev Biol. 2004 Oct 1;274(1):125-38
15355793
Dev Biol. 1977 Mar;56(1):110-56
838129
Mol Cell. 2004 Sep 24;15(6):999-1006
15383288
Mol Cell. 1998 Dec;2(6):741-50
9885562
Cell. 2010 Aug 20;142(4):625-36
20705336
Oncogene. 2003 Nov 24;22(53):8543-67
14634618
Cell. 1997 Aug 8;90(3):405-13
9267021
Cell. 2010 Apr 30;141(3):446-57
20434985
Genes Dev. 1996 Mar 1;10(5):578-91
8598288
Mol Cell. 1999 Sep;4(3):309-19
10518212
Dev Biol. 1979 Jun;70(2):396-417
478167
Cell. 1993 Nov 19;75(4):641-52
8242740
Cell. 1998 May 15;93(4):519-29
9604928
Nat Protoc. 2007;2(3):705-14
17406633
Annu Rev Biochem. 2003;72:291-336
12626338
Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15479-84
20713707
Nat Rev Mol Cell Biol. 2006 Feb;7(2):97-108
16493416
Cell. 1996 Jul 26;86(2):201-8
8706125
Cell. 1999 Aug 6;98(3):317-27
10458607
Nature. 2001 Jul 12;412(6843):198-202
11449278
J Biol Chem. 2008 Jan 18;283(3):1223-7
18024427
J Biol Chem. 1997 Aug 22;272(34):21449-54
9261161
Dev Biol. 1983 Nov;100(1):64-119
6684600
Cell. 1994 Feb 25;76(4):665-76
7907274
EMBO J. 2000 Apr 3;19(7):1625-37
10747030
Mech Dev. 2000 Dec;99(1-2):51-64
11091073
Nature. 2005 Oct 6;437(7060):831-7
16208361
Biochem Soc Trans. 2005 Jun;33(Pt 3):443-6
15916537
Trends Genet. 1998 Oct;14(10):410-6
9820030
Science. 1998 Aug 28;281(5381):1355-7
9721101
Cell. 1994 Sep 9;78(5):739-50
8087842
Bioessays. 2003 Dec;25(12):1147-9
14635248
Development. 2006 Feb;133(4):641-50
16421192
Science. 1997 Feb 21;275(5303):1122-6
9027312
J Intern Med. 2005 Dec;258(6):479-517
16313474
Curr Biol. 1997 Jul 1;7(7):455-60
9210374
Cell. 1986 Mar 28;44(6):817-29
3955651
Mol Cell. 2005 Jul 1;19(1):1-13
15989960
J Biol Chem. 2008 Aug 1;283(31):21315-24
18534987
Cancer Res. 1994 Nov 1;54(21):5501-7
7923184
Science. 1992 Dec 18;258(5090):1955-7
1470921
Dev Biol. 1990 Mar;138(1):33-41
2307287