<b>Molecular properties of the proteasome activator PA28 family proteins and γ‐interferon regulation</b>

Tanahashi, Nobuyuki; Yokota, Kin Ya; Ahn, Joon Young; Chung, Chin Ha; Fujiwara, Tsutomu; Takahashi, Ei; DeMartino, George N.; Slaughter, Clive A.; Toyonaga, Tetsushi; Yamamura, Ken Ichi; Shimbara, Naoki; Tanaka, Keiji

doi:10.1046/j.1365-2443.1997.d01-308.x

Cited by 124 publications

(104 citation statements)

References 49 publications

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“…IFNg increases the levels of both mRNA and protein for PA28a and PA28b (Tanahashi et al, 1997). PA28 is localized in part on PML NBs, the punctuate number and size of the PA28 greatly increase upon IFNg treatment.…”

Section: Pa28mentioning

confidence: 97%

Role and fate of PML nuclear bodies in response to interferon and viral infections

2001

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Interferons (IFNs) are a family of secreted proteins with antiviral, antiproliferative and immunomodulatory activities. The di erent biological actions of IFN are believed to be mediated by the products of speci®cally induced cellular genes in the target cells. The promyelocytic leukaemia (PML) protein localizes both in the nucleoplasm and in matrix-associated multi-protein complexes known as nuclear bodies (NBs). PML is essential for the proper formation and the integrity of the NBs. Modi®cation of PML by the Small Ubiquitin MOdi®er (SUMO) was shown to be required for its localization in NBs. The number and the intensity of PML NBs increase in response to interferon (IFN). Inactivation of the IFN-induced PML gene by its fusion to retinoic acid receptor alpha alters the normal localization of PML from the punctuate nuclear patterns of NBs to microdispersed tiny dots and results in uncontrolled growth in Acute Promyelocytic Leukaemia. The NBs-associated proteins, PML, Sp100, Sp140, Sp110, ISG20 and PA28 are induced by IFN suggesting that nuclear bodies could play a role in IFN response. Although the function of PML NBs is still unclear, some results indicate that they may represent preferential targets for viral infections and that PML could play a role in the mechanism of the antiviral action of IFNs. Viruses, which require the cellular machinery for their replication, have evolved di erent ways to counteract the action of IFN by inhibiting IFN signalling, by blocking the activities of speci®c antiviral mediators or by altering PML expression and/or localization on nuclear bodies. Oncogene (2001) 20, 7274 ± 7286.

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Section: Pa28mentioning

confidence: 97%

Role and fate of PML nuclear bodies in response to interferon and viral infections

2001

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“…It is thought to play an important role in the production of MHC class I antigenic peptides (Groettrup et al, 1996). PA28␥, initially called "Ki antigen," is similar to PA28␣ and ␤ (Kandil et al, 1997;Tanahashi et al, 1997), but forms only homoheptamers and is mostly nuclear. Its functions are poorly characterized, but studies in mice (Murata et al, 1999;Barton et al, 2004) and flies (Masson et al, 2003) suggest a role for this complex in cell cycle progression and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

A Novel Role for PA28γ-Proteasome in Nuclear Speckle Organization and SR Protein Trafficking

Baldin

Militello

Thomas

et al. 2008

MBoC

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“…Possibly, the inserts have some regulatory function. For example, REG␥ has been reported to disappear upon interferon-␥ treatment (30), raising the possibility that the REG␥ insert harbors a degradation signal. As for REG␣ and REG␤, we have observed that KEKE motifs are found in chaperonins such as hsp90 and hsp70 (20).…”

Section: Discussionmentioning

confidence: 99%

Proteasome Activation by REG Molecules Lacking Homolog-specific Inserts

Zhang

Realini

Clawson

et al. 1998

Journal of Biological Chemistry

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The peptidase activities of eukaryotic proteasomes are markedly activated by the 11 S REG or PA28. The three identified REG subunits, designated ␣, ␤, and ␥, differ significantly in sequence over a short span of 15-30 amino acids that we call homolog-specific inserts. These inserts were deleted from each REG to produce the mutant proteins REG␣⌬i, REG␤⌬i, and REG␥⌬i. The purified recombinant proteins were then tested for their ability to oligomerize and activate the proteasome. Both REG␣⌬i and REG␥⌬i formed apparent heptamers and activated human red cell proteasomes to the same extent as their full-length counterparts. By contrast, REG␤⌬i exhibited, at low protein concentrations, reduced proteasome activation when compared with the wild-type REG␤ protein. REG␤⌬i was able to form hetero-oligomers with a single site, monomeric REG␣ mutant and with REG␣⌬i. At low concentrations, the REG␣⌬i/REG␤⌬i hetero-oligomers stimulated the proteasome less than REG␣/REG␤ oligomers formed from wild-type subunits, and the reduced activation by REG␣⌬i/REG␤⌬i was due to removal of the REG␤ insert, not the REG␣ insert. These studies demonstrate that the REG␣ and REG␥ inserts play virtually no role in oligomerization or in proteasome activation. By contrast, removal of REG␤ insert reduces binding of this subunit and REG␣/REG␤ oligomers to proteasomes. On the whole, however, our findings show that REG inserts are not required for binding and activating the proteasome. We speculate that they serve to localize REG-proteasome complexes within cells, possibly by binding components in endoplasmic reticulum membranes.The proteasome is a major proteolytic organelle in the cytosol and nucleus of eukaryotic cells (1-3). The enzyme is a cylindrical structure containing 28 subunits arranged as four rings of seven subunits each. The two end rings are composed of catalytically inactive subunits belonging to the ␣ subunit family based on homology to proteasome subunits from the archebacterium, Thermoplasma. The two central rings are composed of members of the ␤ subunit family (4 -6), some of which are proteolytically active (7). Crystal structures of Thermoplasma and yeast proteasomes reveal that the ␤ subunits form a central proteolytic chamber far from the particle's surface and that entry to this central chamber is greatly restricted (8, 9).By itself, the proteasome does not degrade intact proteins. Association with a 19 S regulatory complex converts the proteasome to the 26 S protease, an energy-dependent enzyme capable of degrading intact proteins (10 -13), including those marked by ubiquitin (14). The proteasome also binds an 11 S protein complex, which we have termed REG and others have named PA28 (15-17). REG binding to the proteasome can stimulate peptide hydrolysis as much as 100-fold. Human red blood cell REG is composed of two ϳ30 KDa subunits, REG␣ and REG␤. These two proteins are closely related to each other and to a third protein, REG␥ (18). The three proteins show extensive sequence similarities, except for a region of 15-32 amino a...

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Molecular properties of the proteasome activator PA28 family proteins and γ‐interferon regulation

Cited by 124 publications

References 49 publications

Role and fate of PML nuclear bodies in response to interferon and viral infections

Role and fate of PML nuclear bodies in response to interferon and viral infections

A Novel Role for PA28γ-Proteasome in Nuclear Speckle Organization and SR Protein Trafficking

Proteasome Activation by REG Molecules Lacking Homolog-specific Inserts

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