Intracellullar peptides as putative natural regulators of protein interactions

被引:62
作者
Ferro, ES
Hyslop, S
Camargo, ACM
机构
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Cell Biol & Dev, Cell Biol Program, Sao Paulo, Brazil
[2] Univ Estadual Campinas, UNICAMP, Fac Med Sci, Dept Pharmacol, Campinas, SP, Brazil
[3] Butantan Inst, Ctr Appl Toxinol, Sao Paulo, Brazil
关键词
antigen presentation; oligopeptidase; phosphorylation; proteasome; signaling; targeting;
D O I
10.1111/j.1471-4159.2004.02757.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Extralysosomal proteolysis by multicatalytic complexes such as the 26S proteasome produces large amounts of peptides in the cytosol, mitochondria and nuclei of eukaryotic cells, and there is increasing evidence that the resulting free intracellular peptides can modulate specific protein interactions. The demonstration that free peptides added to the intracellular milieu can regulate cellular functions mediated by protein interactions suggests new putative roles for these molecules in gene regulation, metabolism, cell signaling and protein targeting. Such interactions frequently involve specific consensus amino acid sequences that can be predicted based on similarities in domain composition. We have recently developed a new strategy for identifying novel natural peptides, the sequences of which correspond to fragments of intracellular proteins and contain putative post-translational modification sites. In this review, we examine the evidence that intracellular peptides released by proteasomes may be involved in regulating protein interactions. In particular, the role of endopeptidase 24.15 (thimet oligopeptidase; EC 3.4.24.15) is discussed in detail as this enzyme has been implicated in intracellular peptide metabolism in vivo in concert with the 26S proteasome.
引用
收藏
页码:769 / 777
页数:9
相关论文
共 87 条
[51]   A SOLUBLE METALLOENDOPEPTIDASE FROM RAT-BRAIN - PURIFICATION OF THE ENZYME AND DETERMINATION OF SPECIFICITY WITH SYNTHETIC AND NATURAL PEPTIDES [J].
ORLOWSKI, M ;
MICHAUD, C ;
CHU, TG .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1983, 135 (01) :81-88
[52]   THE MULTICATALYTIC PROTEINASE COMPLEX, A MAJOR EXTRALYSOSOMAL PROTEOLYTIC SYSTEM [J].
ORLOWSKI, M .
BIOCHEMISTRY, 1990, 29 (45) :10289-10297
[53]  
ORLOWSKI M, 1993, J LAB CLIN MED, V121, P187
[54]   INTRACELLULAR ASPECTS OF PROCESS OF PROTEIN-SYNTHESIS [J].
PALADE, G .
SCIENCE, 1975, 189 (4200) :347-358
[55]   Signaling through scaffold, anchoring, and adaptor proteins [J].
Pawson, T ;
Scott, JD .
SCIENCE, 1997, 278 (5346) :2075-2080
[56]   Assembly of cell regulatory systems through protein interaction domains [J].
Pawson, T ;
Nash, P .
SCIENCE, 2003, 300 (5618) :445-452
[57]   Back to the future with ubiquitin [J].
Pickart, CM .
CELL, 2004, 116 (02) :181-190
[58]   PPARs as therapeutic targets: Reverse cardiology? [J].
Plutzky, J .
SCIENCE, 2003, 302 (5644) :406-407
[59]   Free ATP inhibits thimet oligopeptidase (EC 3.4.24.15) activity, induces autophosphorylation in vitro, and controls oligopeptide degradation in macrophage [J].
Portaro, FCV ;
Hayashi, MAF ;
Silva, CL ;
de Camargo, ACM .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2001, 268 (04) :887-894
[60]   Thimet oligopeptidase and the stability of MHC class I epitopes in macrophage cytosol [J].
Portaro, FCV ;
Gomes, MD ;
Cabrera, A ;
Fernandes, BL ;
Silva, CL ;
Ferro, ES ;
Juliano, L ;
de Camargo, ACM .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 255 (03) :596-601