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Critical Reviews™ in Eukaryotic Gene Expression
IF: 1.841 5-Year IF: 1.927 SJR: 0.649 SNIP: 0.516 CiteScore™: 1.96

ISSN Print: 1045-4403
ISSN Online: 2162-6502

Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukarGeneExpr.v5.i3-4.80
pages 385-436

Regulation and Regulatory Role of Proteinase Inhibitors

R. Michael Roberts
Departments of Animal Sciences and Biochemistry, University of Missouri, 158 Animal Science Research Center, Columbia, MO 65211
Nagappan Mathialagan
Departments of Animal Sciences University of Missouri, 158 Animal Science Research Center, Columbia, MO 65211
Jodie Y. Duffy
Departments of Animal Sciences,University of Missouri ,158 Animal Science Research Center, Columbia, MO 65211
George W. Smith
Departments of Animal Sciences, University of Missouri, 158 Animal Science Research Center, Columbia, MO 65211

ABSTRACT

Excess or ill-timed proteolytic events have, of necessity, to be restrained. Therefore, there are partner proteinase inhibitors to most of the known mammalian enzymes that cleave peptide bonds, a situation that implicates the inhibitors in a myriad of normal as well as pathological processes. Here, what is currently known about the regulatory functions, the mode of action, and the control of gene expression of the commoner extracel-lularly acting proteinase inhibitors is reviewed. The review covers four families of serine proteinase inhibitors: the serpins, the Kunitz, Kazal, and leukoproteinase inhibitors, which overlap considerably in the range of their specificities but differ considerably in their respective structures and likely functions. There then follows a description of the growing family of metalloproteinase inhibitors (usually known by the acronym TIMP), the structurally varied cysteine proteinase inhibitors, and finally α2-macroglobulin, a large multisubunit inhibitor, that is relatively catholic in its range of targets. The review concludes with two short sections, the first an overview of the acute phase response, which features several proteinase inhibitors from the different families discussed earlier, and the second, our prediction of where this research field is headed over the next decade.


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