Home LiteratureArticle Details
PMID: 8255762 Published · ppublish English Journal Article

Specific cleavage of transcription factors by the thiol protease, m-calpain.

Nucleic acids research ·Vol. 21 ·No. 22 ·1993-11-11 ·Pages 5092-100

Watt F, Molloy PL

Abstract

The intracellular nonlysosomal calcium-dependent cysteine protease, m-calpain, is shown to specifically cleave the bHLHzip transcription factor USF leaving the binding and dimerisation domains intact. The resultant protein is capable of efficient DNA binding but is no longer able to activate transcription. A surprisingly high proportion of other transcription factors tested, AP1 (c-Fos/c-Jun), Pit-1, Oct-1, CP1a and b, c-Myc, ATF/CREB, AP2 and AP3 but not Sp1, were similarly cleaved by m-calpain to produce specific partial digestion products. These properties make m-calpain a particularly useful protease for proteolytic studies of transcription factors and also raise the possibility that m-calpain may be involved in vivo in regulation of turnover or transcriptional activity of a number of transcription factors.

MeSH Terms
Base Sequence Calcium/metabolism Calpain/metabolism Cell Line DNA-Binding Proteins Electrophoresis, Polyacrylamide Gel Endopeptidases/metabolism HeLa Cells Humans Molecular Sequence Data Oligodeoxyribonucleotides Substrate Specificity Transcription Factors/metabolism Transcription, Genetic Upstream Stimulatory Factors
Chemicals
DNA-Binding Proteins Oligodeoxyribonucleotides Transcription Factors USF1 protein, human Upstream Stimulatory Factors Endopeptidases Calpain Calcium
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Watt F
CSIRO Division of Biomolecular Engineering, Sydney Laboratory, North Ryde, NSW, Australia.
Molloy P L
References (63)
63 references, click to expand
  1. A unique specificity of a calcium activated neutral protease indicated in histone hydrolysis.
    J Biochem. 1987 Apr;101(4):911-8 PMID: 3038857
  2. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor.
    Cell. 1987 Jun 19;49(6):729-39 PMID: 3034432
  3. A high-efficiency HeLa cell nuclear transcription extract.
    DNA. 1988 Jan-Feb;7(1):47-55 PMID: 3349904
  4. Calpain II involvement in mitosis.
    Science. 1988 May 13;240(4854):911-3 PMID: 2834825
  5. The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins.
    Science. 1988 Jun 24;240(4860):1759-64 PMID: 3289117
  6. c-myc and c-myb protein degradation: effect of metabolic inhibitors and heat shock.
    Mol Cell Biol. 1988 Jun;8(6):2504-12 PMID: 3043180
  7. Analysis of the role of the transcription factor ATF in the assembly of a functional preinitiation complex.
    Cell. 1988 Sep 23;54(7):1043-51 PMID: 3416355
  8. A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype.
    Cell. 1988 Nov 4;55(3):519-29 PMID: 2902928
  9. Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter.
    Genes Dev. 1988 Sep;2(9):1136-43 PMID: 3192075
  10. The POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorhabditis elegans unc-86 gene products.
    Genes Dev. 1988 Dec;2(12A):1513-6 PMID: 3215510
  11. Human CCAAT-binding proteins have heterologous subunits.
    Cell. 1988 Apr 8;53(1):11-24 PMID: 3349524
  12. The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain.
    Genes Dev. 1988 Dec;2(12A):1582-99 PMID: 2905684
  13. Stimulation of transcription from different RNA polymerase II promoters by high mobility group proteins 1 and 2.
    FEBS Lett. 1989 Jan 2;242(2):346-50 PMID: 2464506
  14. Limited proteolysis of protein kinase C subspecies by calcium-dependent neutral protease (calpain).
    J Biol Chem. 1989 Mar 5;264(7):4088-92 PMID: 2537303
  15. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins.
    Cell. 1989 Mar 10;56(5):777-83 PMID: 2493990
  16. Regulation of enzyme levels by proteolysis: the role of pest regions.
    Adv Enzyme Regul. 1988;27:135-51 PMID: 2907964
  17. Regulation of activity of calcium activated neutral protease.
    Adv Enzyme Regul. 1988;27:153-69 PMID: 2854947
  18. Response and binding elements for ligand-dependent positive transcription factors integrate positive and negative regulation of gene expression.
    Cold Spring Harb Symp Quant Biol. 1988;53 Pt 1:545-56 PMID: 3254780
  19. Proteolytic activity associated with the nuclear scaffold. The effect of self-digestion on lamins.
    J Biol Chem. 1989 Sep 5;264(25):15059-65 PMID: 2549049
  20. Autophosphorylation of the type II calmodulin-dependent protein kinase is essential for formation of a proteolytic fragment with catalytic activity. Implications for long-term synaptic potentiation.
    Biochemistry. 1989 Jun 27;28(13):5380-5 PMID: 2550054
  21. Specific proteolysis of the c-mos proto-oncogene product by calpain on fertilization of Xenopus eggs.
    Nature. 1989 Nov 30;342(6249):505-11 PMID: 2555717
  22. Calmodulin-binding proteins as calpain substrates.
    Biochem J. 1989 Sep 15;262(3):693-706 PMID: 2556106
  23. Isovalerylcarnitine is a specific activator of the high calcium requiring calpain forms.
    Biochem Biophys Res Commun. 1990 Feb 28;167(1):373-80 PMID: 2310400
  24. Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers.
    Genes Dev. 1989 Dec;3(12B):2083-90 PMID: 2516827
  25. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins.
    Cell. 1990 Apr 6;61(1):49-59 PMID: 2156629
  26. Calpain II-dependent solubilization of a nuclear protein kinase at micromolar calcium concentrations.
    Biochem Biophys Res Commun. 1990 Apr 30;168(2):589-95 PMID: 2334424
  27. Identification of the proteolytically activated form of protein kinase C in stimulated human neutrophils.
    Proc Natl Acad Sci U S A. 1990 May;87(10):3705-7 PMID: 2339114
  28. DNA-binding and transcriptional properties of human transcription factor TFIID after mild proteolysis.
    Mol Cell Biol. 1990 Jul;10(7):3415-20 PMID: 2192257
  29. Physical characterization of the purified CCAAT transcription factor, alpha-CP1.
    J Biol Chem. 1990 Aug 5;265(22):13362-9 PMID: 2376599
  30. Calcium and cell cycle control.
    Development. 1990 Apr;108(4):525-42 PMID: 2167196
  31. The major transcriptional regulatory protein of herpes simplex virus type 1 includes a protease resistant DNA binding domain.
    Nucleic Acids Res. 1990 Aug 11;18(15):4579-85 PMID: 2167472
  32. The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer.
    Genes Dev. 1990 Oct;4(10):1730-40 PMID: 2249772
  33. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53.
    Cell. 1990 Dec 21;63(6):1129-36 PMID: 2175676
  34. Degradation of nuclear oncoproteins by the ubiquitin system in vitro.
    Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):139-43 PMID: 1846034
  35. Isolation of human brain protein kinase C: evidence for kinase C catalytic fragment modulating G protein-GTPase activity.
    Biochem Biophys Res Commun. 1991 Jan 31;174(2):593-9 PMID: 1899569
  36. Comparison of the autolyzed and unautolyzed forms of mu- and m-calpain from bovine skeletal muscle.
    Biochim Biophys Acta. 1991 Apr 8;1077(2):197-208 PMID: 2015293
  37. Eukaryotic protein degradation.
    Curr Opin Cell Biol. 1990 Dec;2(6):1143-9 PMID: 1966008
  38. Proteolysis of nuclear proteins by mu-calpain and m-calpain.
    J Biol Chem. 1991 Jul 25;266(21):13920-4 PMID: 1649832
  39. Degradation of transcription factors, c-Jun and c-Fos, by calpain.
    FEBS Lett. 1991 Aug 5;287(1-2):57-61 PMID: 1908791
  40. Recombinant 43-kDa USF binds to DNA and activates transcription in a manner indistinguishable from that of natural 43/44-kDa USF.
    Mol Cell Biol. 1991 Oct;11(10):5125-36 PMID: 1922036
  41. Max: functional domains and interaction with c-Myc.
    Genes Dev. 1992 Jan;6(1):81-92 PMID: 1730412
  42. H1 histone stimulates limited proteolysis of protein kinase C subspecies by calpain II.
    J Biochem. 1991 Sep;110(3):364-8 PMID: 1769964
  43. Specific increase in calcium-activated neutral protease with low calcium sensitivity (m-calpain) in proerythroblastic K562 cell line cells induced to differentiation by phorbol 12-myristate 13-acetate.
    Exp Cell Res. 1992 Jun;200(2):513-22 PMID: 1572412
  44. The regulation of transcription by phosphorylation.
    Cell. 1992 Aug 7;70(3):375-87 PMID: 1643656
  45. Definition of the transcriptional activation domain of recombinant 43-kilodalton USF.
    Mol Cell Biol. 1992 Nov;12(11):5094-101 PMID: 1406684
  46. A comparison of the intracellular distribution of mu-calpain, m-calpain, and calpastatin in proliferating human A431 cells.
    Exp Cell Res. 1992 Nov;203(1):5-16 PMID: 1426051
  47. m-Calpain requires DNA for activity on nuclear proteins at low calcium concentrations.
    J Biol Chem. 1993 Jan 5;268(1):653-7 PMID: 8416968
  48. Is calpain activity regulated by membranes and autolysis or by calcium and calpastatin?
    Bioessays. 1992 Aug;14(8):549-56 PMID: 1365908
  49. Estrogen binding proteins of calf uterus. Molecular and functional characterization of the receptor transforming factor: A Ca2+-activated protease.
    J Biol Chem. 1977 Feb 25;252(4):1358-66 PMID: 838720
  50. Progesterone-binding components of chick oviduct: partial purification and characterization of a calcium-activated protease which hydrolyzes the progesterone receptor.
    Biochemistry. 1980 Jan 22;19(2):335-43 PMID: 6986169
  51. DNA-dependent transcription of adenovirus genes in a soluble whole-cell extract.
    Proc Natl Acad Sci U S A. 1980 Jul;77(7):3855-9 PMID: 6933441
  52. Limited autolysis reduces the Ca2+ requirement of a smooth muscle Ca2+-activated protease.
    J Biol Chem. 1982 Aug 10;257(15):9072-7 PMID: 6284756
  53. Separation and characterization of factors mediating accurate transcription by RNA polymerase II.
    J Biol Chem. 1982 Dec 10;257(23):14419-27 PMID: 7142220
  54. Purification of human platelet calcium-activated protease. Effect on platelet and endothelial function.
    J Biol Chem. 1983 Jun 10;258(11):7168-74 PMID: 6304081
  55. Effect of L-alpha-phosphatidylinositol on a vascular smooth muscle Ca2+-dependent protease. Reduction of the Ca2+ requirement for autolysis.
    J Biol Chem. 1984 Oct 10;259(19):11627-30 PMID: 6090440
  56. Two distinct transcription factors bind to the HSV thymidine kinase promoter in vitro.
    Cell. 1985 Sep;42(2):559-72 PMID: 2992804
  57. Bidirectional SV40 transcription mediated by tandem Sp1 binding interactions.
    Science. 1985 Nov 1;230(4725):511-7 PMID: 2996137
  58. An RNA polymerase II transcription factor binds to an upstream element in the adenovirus major late promoter.
    Cell. 1985 Dec;43(2 Pt 1):439-48 PMID: 4075400
  59. Identification of a factor in HeLa cells specific for an upstream transcriptional control sequence of an EIA-inducible adenovirus promoter and its relative abundance in infected and uninfected cells.
    Proc Natl Acad Sci U S A. 1986 Aug;83(16):5914-8 PMID: 2942943
  60. Purification and biochemical characterization of the promoter-specific transcription factor, Sp1.
    Science. 1986 Oct 3;234(4772):47-52 PMID: 3529394
  61. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis.
    Science. 1986 Oct 17;234(4774):364-8 PMID: 2876518
  62. Hydrophobic association of calpains with subcellular organelles. Compartmentalization of calpains and the endogenous inhibitor calpastatin in tissues.
    J Biol Chem. 1986 Oct 25;261(30):13936-42 PMID: 3021722
  63. Purification and characterization of OTF-1, a transcription factor regulating cell cycle expression of a human histone H2b gene.
    Cell. 1987 Dec 4;51(5):773-81 PMID: 3677172
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/21.22.5092
Published
1993-11-11
Pages
5092-100
Language
English
Region
England
NLM ID
0411011
PMCID
PMC310622
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/21.22.5092 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2