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C-terminal binding proteins (CtBPs) are transcriptional co-repressors that are subject to proteasome-dependent downregulation during apoptosis. Alternative mechanisms that regulate CtBP expression are currently under investigation and the role of CtBPs in neuronal survival is largely unexplored. Here, we show that CtBPs are downregulated in cerebellar granule neurons (CGNs) induced to undergo apoptosis by a variety of stressors. Moreover, antisense-mediated downregulation of CtBP1 is sufficient to cause CGN apoptosis. Similarly, the CtBP inhibitor, 4-methylthio-2-oxobutyric acid, induces expression of the CtBP target Noxa and causes actinomycin-sensitive CGN apoptosis. Unexpectedly, we found that the mechanism of CtBP downregulation in CGNs undergoing apoptosis varies in a stimulus-specific manner involving either the proteasome or caspases. In the case of CGNs deprived of depolarizing potassium (5K apoptotic condition), caspases appear to play a dominant role in CtBP downregulation. However, incubation in 5K does not enhance the kinetics of CtBP1 degradation and recombinant CtBP1 is not cleaved in vitro by caspase-3. In addition, 5K has no significant effect on CtBP transcript expression. Finally, mouse embryonic stem cells display caspase-dependent downregulation of CtBP1 following exposure to staurosporine, an effect that is not observed in DGCR8 knockout cells which are deficient in miRNA processing. These data identify caspase-dependent downregulation of CtBPs as an alternative mechanism to the proteasome for regulation of these transcriptional co-repressors in neurons undergoing apoptosis. Moreover, caspases appear to regulate CtBP expression indirectly, at a post-transcriptional level, and via a mechanism that is dependent upon miRNA processing. We conclude that CtBPs are essential pro-survival proteins in neurons and their downregulation contributes significantly to neuronal apoptosis via the de-repression of pro-apoptotic genes.

Titel:	C-terminal binding proteins are essential pro-survival factors that undergo caspase-dependent downregulation during neuronal apoptosis.
Autor/in / Beteiligte Person:	Stankiewicz, TR ; Schroeder, EK ; Kelsey, NA ; Bouchard, RJ ; Linseman, DA
Zeitschrift:	Molecular and cellular neurosciences, Jg. 56 (2013-09-01), S. 322-332
Veröffentlichung:	San Diego : Academic Press, c1990-, 2013
Medientyp:	academicJournal
ISSN:	1095-9327 (electronic)
DOI:	10.1016/j.mcn.2013.07.004
Schlagwort:	Animals Carrier Proteins antagonists & inhibitors Carrier Proteins genetics Caspase 3 metabolism Female Male Methionine analogs & derivatives Methionine pharmacology Neurons drug effects Neurons physiology Potassium pharmacology Proto-Oncogene Proteins c-bcl-2 genetics Proto-Oncogene Proteins c-bcl-2 metabolism Rats Rats, Sprague-Dawley Staurosporine pharmacology Transcription Factors antagonists & inhibitors Transcription Factors genetics Apoptosis Carrier Proteins metabolism Down-Regulation Neurons metabolism Transcription Factors metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Language: English [Mol Cell Neurosci] 2013 Sep; Vol. 56, pp. 322-332. <i>Date of Electronic Publication: </i>2013 Jul 13. MeSH Terms: Apoptosis* ; Down-Regulation* ; Carrier Proteins / metabolism ; Neurons / metabolism ; Transcription Factors / *metabolism ; Animals ; Carrier Proteins / antagonists & inhibitors ; Carrier Proteins / genetics ; Caspase 3 / metabolism ; Female ; Male ; Methionine / analogs & derivatives ; Methionine / pharmacology ; Neurons / drug effects ; Neurons / physiology ; Potassium / pharmacology ; Proto-Oncogene Proteins c-bcl-2 / genetics ; Proto-Oncogene Proteins c-bcl-2 / metabolism ; Rats ; Rats, Sprague-Dawley ; Staurosporine / pharmacology ; Transcription Factors / antagonists & inhibitors ; Transcription Factors / genetics References: Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10467-71. (PMID: 7479821) ; J Mol Biol. 2010 May 21;398(5):657-71. (PMID: 20361981) ; Mol Cell Biol. 2006 Jul;26(13):4882-94. (PMID: 16782877) ; Adv Exp Med Biol. 2010;700:56-66. (PMID: 21627030) ; J Biol Chem. 1996 Apr 26;271(17):10149-53. (PMID: 8626575) ; Int J Biol Sci. 2011 Jan 27;7(1):133-7. (PMID: 21278922) ; J Biol Chem. 2006 Nov 17;281(46):34810-5. (PMID: 16984892) ; PLoS One. 2012;7(3):e33156. (PMID: 22427977) ; Cell Cycle. 2011 Jun 1;10(11):1845-52. (PMID: 21543894) ; Mol Cell Biol. 2006 Nov;26(21):8202-13. (PMID: 16940173) ; Mol Cell Biol. 2002 Aug;22(15):5296-307. (PMID: 12101226) ; Nat Genet. 2007 Mar;39(3):380-5. (PMID: 17259983) ; Biochem Biophys Res Commun. 2003 Feb 7;301(2):521-8. (PMID: 12565893) ; Cell. 2003 Oct 17;115(2):177-86. (PMID: 14567915) ; Toxicol Appl Pharmacol. 2011 Nov 1;256(3):314-23. (PMID: 21846476) ; BMC Syst Biol. 2011 Aug 25;5:136. (PMID: 21867514) ; Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2802-7. (PMID: 15708980) ; Apoptosis. 2006 Jun;11(6):879-88. (PMID: 16547590) ; J Neurochem. 2006 May;97(4):957-67. (PMID: 16686690) ; Mol Cell. 2002 Oct;10(4):857-69. (PMID: 12419229) ; Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6683-8. (PMID: 10359772) ; J Neurochem. 2005 Aug;94(4):1025-39. (PMID: 16092944) ; Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10989-93. (PMID: 8248201) ; FASEB J. 1999 Feb;13(2):339-46. (PMID: 9973322) ; Cell Death Differ. 2010 Mar;17(3):513-21. (PMID: 19798104) ; Science. 2002 Mar 8;295(5561):1895-7. (PMID: 11847309) ; Nat Neurosci. 2006 Nov;9(11):1382-7. (PMID: 17041593) ; Biochem Biophys Res Commun. 2012 Jan 6;417(1):175-81. (PMID: 22138398) ; Nature. 1995 Jun 8;375(6531):500-3. (PMID: 7777059) ; J Biol Chem. 2001 Oct 19;276(42):39123-31. (PMID: 11509562) ; J Biol Chem. 2001 Dec 21;276(51):48262-8. (PMID: 11590170) ; Nat Genet. 2002 Apr;30(4):363-4. (PMID: 11896390) ; J Neurochem. 2006 Aug;98(4):1290-301. (PMID: 16787403) ; Oncogene. 2000 Aug 3;19(33):3823-8. (PMID: 10949939) ; Cancer Res. 2005 May 1;65(9):3509-12. (PMID: 15867338) ; Dev Dyn. 2006 Feb;235(2):490-5. (PMID: 16258936) ; J Biol Chem. 2012 May 11;287(20):16835-48. (PMID: 22378792) ; EMBO Rep. 2008 Jun;9(6):582-9. (PMID: 18483486) ; EMBO J. 1998 Sep 1;17(17):5129-40. (PMID: 9724649) ; Nat Struct Mol Biol. 2005 May;12(5):423-8. (PMID: 15834423) ; Biochem Biophys Res Commun. 2010 Sep 24;400(3):396-402. (PMID: 20800578) ; Cell Cycle. 2010 Sep 15;9(18):3740-50. (PMID: 20930544) ; Mol Cell Biol. 2006 Mar;26(6):2360-72. (PMID: 16508011) ; Nat Commun. 2011 Nov 08;2:529. (PMID: 22068596) ; Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):12119-24. (PMID: 21730158) ; Cell. 1995 Jun 2;81(5):801-9. (PMID: 7774019) ; Cancer Res. 2008 Mar 1;68(5):1362-8. (PMID: 18316599) ; Genes Chromosomes Cancer. 2004 Sep;41(1):56-64. (PMID: 15236317) ; Dev Biol. 2008 Nov 1;323(1):64-75. (PMID: 18773887) ; Biochim Biophys Acta. 2011 Nov-Dec;1809(11-12):686-93. (PMID: 21640212) ; Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9202-7. (PMID: 12872005) ; Neurotox Res. 2011 Apr;19(3):374-88. (PMID: 20333497) ; FEBS Lett. 2007 Nov 13;581(27):5241-6. (PMID: 17964573) ; J Mol Biol. 2011 Apr 29;408(2):262-76. (PMID: 21354178) ; J Neurosci. 2002 Nov 1;22(21):9287-97. (PMID: 12417654) ; Brain Res. 2000 Jun 2;866(1-2):33-43. (PMID: 10825478) ; Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4568-73. (PMID: 12676992) ; Mol Cell Biol. 2008 Jan;28(1):269-81. (PMID: 17967884) ; Mech Dev. 2009 Jan-Feb;126(1-2):68-79. (PMID: 18992810) Grant Information: R01 NS062766 United States NS NINDS NIH HHS Contributed Indexing: Keywords: 4,6-diamidino-2-phenylidole; 4-methylthio-2-oxobutyric; 6-OHDA; 6-hydroxydopamine; AD; Anti; B-cell lymphoma-3; BKLF; Bcl-3; C-terminal binding protein; C-terminal binding proteins (CtBPs); CCD; CGNs; Caspase-3; Con; CtBP; DAPI; DGCR8; DiGeorge critical region 8; EP; G protein-coupled receptor kinase-interacting protein-z-short; GITz-short; Inv; KO; LTox; MEFs; MPP(+); MTOB; Neuronal apoptosis; PARP; PBS; PCR; RNA silencing suppressor; RSS; SNP; STS; Tox B; Toxin B; WT; actinomycin D; basic Krüppel-like factor; cerebellar granule neurons; charge-coupled device; control; dCtBP; drosophila CtBP; endoporter; inverse; knockout; lethal toxin; mESCs; methyl-4-phenylpyridinium; miRNA; micro RNA; morpholino-antisense oligonucleotides; mouse embryonic stem cells; murine embryonic fibroblasts; phosphate buffer saline; poly-(ADP-ribose) polymerase; polymerase chain reaction; rCasp3; recombinant caspase-3; sodium nitroprusside; staurosporine; wild type Substance Nomenclature: 0 (Carrier Proteins) ; 0 (Ctbp1 protein, rat) ; 0 (Pmaip1 protein, rat) ; 0 (Proto-Oncogene Proteins c-bcl-2) ; 0 (Transcription Factors) ; 583-92-6 (2-keto-4-methylthiobutyric acid) ; AE28F7PNPL (Methionine) ; EC 3.4.22.- (Caspase 3) ; H88EPA0A3N (Staurosporine) ; RWP5GA015D (Potassium) Entry Date(s): Date Created: 20130718 Date Completed: 20140620 Latest Revision: 20211021 Update Code: 20240513 PubMed Central ID: PMC3791214

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C-terminal binding proteins are essential pro-survival factors that undergo caspase-dependent downregulation during neuronal apoptosis.