Analysis of mammalian 20S proteasome biogenesis: the maturation of beta-subunits is an ordered two-step mechanism involving autocatalysis.

Schmidtke, Gunter; Kraft, Regine; Kostka, Susanne; Henklein, Peter; Frömmel, Cornelius; Löwe, Jan; Huber, Robert; Kloetzel, Peter M.; Schmidt, Marion

doi:10.1002/j.1460-2075.1996.tb01081.x

Cited by 184 publications

(177 citation statements)

References 61 publications

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“…In fact, proteasome inactivation has been shown to delay the autocatalytic processing step necessary for the final maturation step of the 20 S core complex (10,11,34,35). Therefore, the observed increase in the amount of proteasome subunits may in part be explained by the accumulation of proteasome precursor complexes (Fig.…”

Section: Up-regulation Of Proteasomal Mrnas Results In De Novo Formatmentioning

confidence: 99%

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Inhibition of Proteasome Activity Induces Concerted Expression of Proteasome Genes and de Novo Formation of Mammalian Proteasomes

Meiners¹,

Heyken

Weller³

et al. 2003

Journal of Biological Chemistry

292

215

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The 26 S proteasome is a high molecular mass proteinase complex that is built by at least 32 different protein subunits. Such protease complexes in bacteria and yeast are systems that undergo a highly sophisticated network of gene expression regulation. However, regulation of mammalian proteasome gene expression has been neglected so far as a possible control mechanism for the amount of proteasomes in the cell. Here, we show that treatment of cells with proteasome inhibitors and the concomitant impairment of proteasomal enzyme activity induce a transient and concerted up-regulation of all mammalian 26 S proteasome subunit mRNAs. Proteasome inhibition in combination with inhibition of transcription revealed that the observed up-regulation is mediated by coordinated transcriptional activation of the proteasome genes and not by post-transcriptional events. Our experiments also demonstrate that inhibitor-induced proteasome gene activation results in enhanced de novo protein synthesis of all subunits and in increased de novo formation of proteasomes. This phenomenon is accompanied by enhanced expression of the proteasome maturation factor POMP. Thus, our experiments present the first evidence that the amount of proteasomes in mammalia is regulated at the transcriptional level and that there exists an autoregulatory feedback mechanism that allows the compensation of reduced proteasome activity.

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Section: Up-regulation Of Proteasomal Mrnas Results In De Novo Formatmentioning

confidence: 99%

“…These propeptides play an essential role during the biogenesis process and are processed by cis-or transautocatalysis in a two-step mechanism (10). The propeptides of the active ␤ subunits are cleaved off autocatalytically, whereas the propeptides of the inactive subunits are removed by their active neighbors (10 -13).…”

mentioning

confidence: 99%

Inhibition of Proteasome Activity Induces Concerted Expression of Proteasome Genes and de Novo Formation of Mammalian Proteasomes

Meiners¹,

Heyken

Weller³

et al. 2003

Journal of Biological Chemistry

292

215

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show abstract

“…The seven human alpha subunit cDNAs were amplified by RT-PCR and cloned in frame into the following vectors pET41 (Novagen), pCITE (Novagen), pGBT9 and pGAD GH (Clontech), generating constructs pET41-a 1-7 , pCITE-a 1-7 , pGBT9-a [1][2][3][4][5][6][7] and pGAD GH-a [1][2][3][4][5][6][7] . All constructs used in the study were sequenced to confirm identity and PCR fidelity.…”

Section: Preparation Of Expression Vectorsmentioning

confidence: 99%

The α4 and α7 subunits and assembly of the 20S proteasome

et al. 2004

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The detailed mechanism of eukaryotic 20S proteasome assembly is currently unknown. In the present study, we demonstrate that the 20S proteasome subunits a4 and a7 interact with each other as well as all the a-subunits in vivo and in vitro. The N-terminal parts of a4 and a7 are essential for these newly discovered interactions in vitro. Glycerol gradient centrifugation of soluble extracts of HEK293 cells and Western blot analyses show that several a-subunits are found in non-proteasomal lowdensity fractions. The a4 and a7 subunits co-immunoprecipitate together from these low-density fractions. The unexpected interaction between a4 and a7 may provide a molecular basis for the formation of previously reported 13S and 16S assembly intermediates.

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“…We previously showed that assembly of mammalian 20S proteasomes is a multistep process that occurs via the formation of distinct proteasome precursor complexes with different ␤ subunit compositions. Active-site ␤ subunits are synthesized and incorporated as proproteins that essentially mature by a two-step procedure within the precursor complexes (12,13). Final activation of the ␤ subunits requires the formation of the preholoproteasome assembly intermediate.…”

mentioning

confidence: 99%

IFN-γ-induced immune adaptation of the proteasome system is an accelerated and transient response

Heink

Ludwig

Kloetzel

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

254

249

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Peptide generation by the proteasome is rate-limiting in MHC class I-restricted antigen presentation in response to IFN-␥. IFN-␥-induced de novo formation of immunoproteasomes, therefore, essentially supports the rapid adjustment of the mammalian immune system. Here, we report that the molecular interplay between the proteasome maturation protein (POMP) and the proteasomal ␤5i subunit low molecular weight protein 7 (LMP7) has a key position in this immune adaptive program. IFN-␥-induced coincident biosynthesis of POMP and LMP7 and their direct interaction essentially accelerate immunoproteasome biogenesis compared with constitutive 20S proteasome assembly. The dynamics of this process is determined by rapid LMP7 activation and the immediate LMP7-dependent degradation of POMP. Silencing of POMP expression impairs recruitment of both ␤5 subunits into the proteasome complex, resulting in decreased proteasome activity, reduced MHC class I surface expression, and induction of apoptosis. Furthermore, our data reveal that immunoproteasomes exhibit a considerably shortened half-life, compared with constitutive proteasomes. In consequence, our studies demonstrate that the cytokine-induced rapid immune adaptation of the proteasome system is a tightly regulated and transient response allowing cells to return rapidly to a normal situation once immunoproteasome function is no longer required.antigen presentation ͉ immunoproteasome ͉ MHC class I

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Analysis of mammalian 20S proteasome biogenesis: the maturation of beta-subunits is an ordered two-step mechanism involving autocatalysis.

Cited by 184 publications

References 61 publications

Inhibition of Proteasome Activity Induces Concerted Expression of Proteasome Genes and de Novo Formation of Mammalian Proteasomes

Inhibition of Proteasome Activity Induces Concerted Expression of Proteasome Genes and de Novo Formation of Mammalian Proteasomes

The α4 and α7 subunits and assembly of the 20S proteasome

IFN-γ-induced immune adaptation of the proteasome system is an accelerated and transient response

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