Publication: The role of the proteasome in cellular protein degradation
Authors
Driscoll, J.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Eukaryotic cells contain a major intracellular
proteolytic activity known as the proteasome. The
proteasome is a strongly conserved cylindrical structure
of high molecular weight (650 kDa, -20 S) and
desmonstrates multiple endopeptidase activities. The
general structural, biochemical and genetic features of
the proteasonie are conserved from archaebacteria
through yeast to humans. This structure fulfills an
essential role by functioning as the proteolytic core of a
26 S multienzyme complex responsible for the energydependent
degradation of ubiquitinated proteins. The
bulk of intracellular proteolysis appears to be through
the ubiquitin-dependent pathway. Incorporation of the
proteasome into the 26 S niultienzyme complex appears
to confer both a specificity for ubiquitinated proteins as
well as a nieans to tightly regulate proteolytic activity.
Thus, one function of the proteasome is required for the
degradation of either abnormal or certain regulatory
proteins by the ubiquitin pathway. Proteasoine subunits
appear to be encoded by a related gene family as defined
by extensive sequence similarities. The gene products
are confined to either of two general classes: a-type
which appear to be structural and 8-type which may be
catalytic. Genes encoding at least two proteasome
subunits map to the Ma-jor Histocompatibility Complex.
Accurnulating evidence points to the proteasome (or a
specialized form) participatirig in the cytosolic degradation of these viral proteins upon cellular
infection. Through a previously unforseen mechanisin. it
appears that the products from the digestion of the viral
proteins may be rescued from further digestion to amino
acids and shuttled from the cytoplasm through the
endoplasniic reticulum to the cell surface where they
serve as antigenic peptides for recognition by the
immune system. The proteasome may have been
recruited by the immune system to serve as the cytosolic activity responsible for generating these antigenic
peptides. The proteasome may function in the ubiquitindependent
degradation of not only certain self-proteins
but may fulfill a second essential role in the degradation
of proteins originating from viral infection
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