Calpain-2 participates in the process of calpain-1 inactivation.
autolysis
calpains
inhibition mechanism
proteolysis
regulation
substrate specificity
Journal
Bioscience reports
ISSN: 1573-4935
Titre abrégé: Biosci Rep
Pays: England
ID NLM: 8102797
Informations de publication
Date de publication:
27 11 2020
27 11 2020
Historique:
received:
29
02
2020
revised:
18
09
2020
accepted:
20
10
2020
pubmed:
21
10
2020
medline:
13
4
2021
entrez:
20
10
2020
Statut:
ppublish
Résumé
Calpain-1 and calpain-2 are highly structurally similar isoforms of calpain. The calpains, a family of intracellular cysteine proteases, cleave their substrates at specific sites, thus modifying their properties such as function or activity. These isoforms have long been considered to function in a redundant or complementary manner, as they are both ubiquitously expressed and activated in a Ca2+- dependent manner. However, studies using isoform-specific knockout and knockdown strategies revealed that each calpain species carries out specific functions in vivo. To understand the mechanisms that differentiate calpain-1 and calpain-2, we focused on the efficiency and longevity of each calpain species after activation. Using an in vitro proteolysis assay of troponin T in combination with mass spectrometry, we revealed distinctive aspects of each isoform. Proteolysis mediated by calpain-1 was more sustained, lasting as long as several hours, whereas proteolysis mediated by calpain-2 was quickly blunted. Calpain-1 and calpain-2 also differed from each other in their patterns of autolysis. Calpain-2-specific autolysis sites in its PC1 domain are not cleaved by calpain-1, but calpain-2 cuts calpain-1 at the corresponding position. Moreover, at least in vitro, calpain-1 and calpain-2 do not perform substrate proteolysis in a synergistic manner. On the contrary, calpain-1 activity is suppressed in the presence of calpain-2, possibly because it is cleaved by the latter protein. These results suggest that calpain-2 functions as a down-regulation of calpain-1, a mechanism that may be applicable to other calpain species as well.
Identifiants
pubmed: 33078830
pii: 226716
doi: 10.1042/BSR20200552
pmc: PMC7610153
pii:
doi:
Substances chimiques
Troponin T
0
Calpain
EC 3.4.22.-
CAPN1 protein, human
EC 3.4.22.52
CAPN2 protein, human
EC 3.4.22.53
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 The Author(s).
Références
J Biochem. 1978 Jul;84(1):225-30
pubmed: 29038
Nature. 2008 Nov 20;456(7220):404-8
pubmed: 19020622
J Biochem. 2012 Apr;151(4):417-22
pubmed: 22232565
Mol Cell Biol. 2011 Oct;31(19):4097-106
pubmed: 21791606
J Biol Chem. 2019 Sep 6;294(36):13396-13410
pubmed: 31324722
J Biol Chem. 1983 Jul 25;258(14):8883-9
pubmed: 6306001
J Biochem. 1986 Jul;100(1):183-90
pubmed: 3020013
Electrophoresis. 2001 Apr;22(6):1004-7
pubmed: 11358120
Mol Cell Biol. 2001 Mar;21(6):2213-20
pubmed: 11238954
J Physiol. 2008 Jul 15;586(14):3537-50
pubmed: 18556368
Exp Cell Res. 2004 Sep 10;299(1):179-87
pubmed: 15302585
Curr Neuropharmacol. 2019;17(9):823-829
pubmed: 30819083
Biochim Biophys Acta Proteins Proteom. 2020 Jul;1868(7):140411
pubmed: 32200007
J Biol Chem. 2016 Dec 30;291(53):27313-27322
pubmed: 27881674
Am J Physiol Cell Physiol. 2008 Apr;294(4):C957-65
pubmed: 18216163
FEBS Lett. 1993 May 3;322(1):65-8
pubmed: 8482370
J Biol Chem. 1996 Dec 27;271(52):33161-4
pubmed: 8969168
Cell Rep. 2016 Jun 28;16(1):79-91
pubmed: 27320912
Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):588-92
pubmed: 10639123
Physiol Rev. 2003 Jul;83(3):731-801
pubmed: 12843408
BMC Dev Biol. 2006 Jan 24;6:3
pubmed: 16433929
Biochim Biophys Acta. 1991 Jun 24;1078(2):192-8
pubmed: 2065086
Cell. 2002 Mar 8;108(5):649-60
pubmed: 11893336
J Mol Evol. 2001 Sep;53(3):191-203
pubmed: 11523006
J Biol Chem. 1993 Apr 5;268(10):7422-6
pubmed: 8463275
J Biochem. 2001 Nov;130(5):605-11
pubmed: 11686922
Biochim Biophys Acta. 2011 Jul;1814(7):864-72
pubmed: 21549862
World J Gastroenterol. 2020 Apr 7;26(13):1450-1462
pubmed: 32308346
Biochem J. 1995 May 15;308 ( Pt 1):57-61
pubmed: 7755588
Gene. 2016 May 10;582(1):1-13
pubmed: 26774798
Genes Cells. 2013 Sep;18(9):753-63
pubmed: 23786391
Environ Health Perspect. 2019 Jul;127(7):77003
pubmed: 31274337
PLoS One. 2011 May 03;6(5):e19035
pubmed: 21559271
Mol Cell Proteomics. 2016 Apr;15(4):1262-80
pubmed: 26796116
Biochem J. 2016 Sep 15;473(18):2893-909
pubmed: 27402795
Biochem J. 2012 Nov 1;447(3):335-51
pubmed: 23035980
Nat Struct Biol. 2003 May;10(5):371-8
pubmed: 12665854
Biochemistry. 2006 Sep 26;45(38):11681-94
pubmed: 16981728
PLoS One. 2012;7(3):e33468
pubmed: 22432027
PLoS One. 2013 May 31;8(5):e64627
pubmed: 23741357
Cancer Med. 2018 Jan;7(1):175-183
pubmed: 29210197
Biochimie. 2016 Mar;122:169-87
pubmed: 26363099
Nucleic Acids Res. 2017 Jan 4;45(D1):D1107-D1111
pubmed: 27899654
J Mol Biol. 2004 Nov 5;343(5):1313-26
pubmed: 15491615
J Biol Chem. 1997 Apr 25;272(17):11268-75
pubmed: 9111030
Nature. 2008 Nov 20;456(7220):409-12
pubmed: 19020623