Abstracts (complete list) - Wissenschaft Online

Thorsten Joeris, Petra Krienke, Ulrike Kuckelkorn, S.H.E. Kaufmann, Ulrich Steinhoff
Proteasome assembly: Competitive integration of constitutive
and IFNγ inducible catalytic subunits
Proteasomes are multicatalytic protease complexes responsible for non-lysosomal
degradation of proteins. In vertebrates 20S proteasomes occur in two major forms:
constitutive proteasomes (c20S) and the IFNγ inducible immunoproteasomes (i20S).
The two forms differ in their catalytically active subunits and consequently in their
overall specificity and activity. Due to the diverse effects of proteasome composition on
multiple cellular processes, it is of interest to understand the basic mechanisms of c20S
and i20S formation. So far, formation of i20S is believed to be a result of cooperative
integration of the IFNγ inducible subunits β1i, β2i and β5i. According to this concept β5i
is necessary for processing of β1i and β2i precursor subunits during proteasome
assembly. Here, we analyse the formation of 20S proteasomes during infection of WT
and β5i deficient (lmp7 -/- ) mice with Listeria monocytogens. In lmp7 -/- mice β5 can
easily process β1i and β2i resulting in the formation of mixed proteasomes (m20S). The
observed accumulation of unprocessed β1i and β2i in precursor proteasomes is caused
by a lack of β5 subunits and not by its inability to pair with β1i and β2i. As β5 is not
upregulated by infection, it can not compensate the absence of β5i in lmp7 -/- mice. Our
in vivo data question the current model of cooperative i20S formation. Instead, we
provide evidence that the mechanism underlying i20S formation is substantially
regulated by simultaneous overexpression of IFNγ inducible subunits, which enables
them to outcompete the constitutive subunits at protein level during proteasome
assembly.