cDNA Cloning and Interferon γ Down-Regulation of Proteasomal Aubunits X and Y

Akiyama, Kinya; Yokota, Kim-Ya; Kagawa, Shunsuke; Shimbara, Naoki; Tamura, Tomohiro; Akioka, Hiroshi; Nothwang, Hans Gerd; Noda, Chiseko; Tanaka, Keiji; Ichihara, Akira

doi:10.1126/science.8066462

Cited by 180 publications

(115 citation statements)

References 27 publications

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“…Nevertheless, there is some evidence that alterations in proteasome function are also subject to regulation. For example, y-interferon enhances antigen processing and presentation (Akiyama et al, 1994). Among the effects of these modulators is the up-regulation of specific proteasome subunits encoded in the major histocompatibility complex.…”

Section: Discussionmentioning

confidence: 99%

Yeast counterparts of subunits S5a and p58 (S3) of the human 26S proteasome are encoded by two multicopy suppressors of nin1-1.

Kominami

Okura

Kawamura

et al. 1997

MBoC

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Ninlp, a component of the 26S proteasome of Saccharomyces cerevisiae, is required for activation of Cdc28p kinase at the G1-S-phase and G2-M boundaries. By exploiting the temperature-sensitive phenotype of the ninl-l mutant, we have screened for genes encoding proteins with related functions to Ninlp and have cloned and characterized two new multicopy suppressors, SUNI and SlUN2, of the ninl-l mutation. SUNI can suppress a null ninl mutation, whereas SlUN2, an essential gene, does not. Sunlp is a 268-amino acid protein which shows strong similarity to MBP1 of Arabidopsis thaliana, a homologue of the S5a subunit of the human 26S proteasome. Sunlp binds ubiquitin-lysozyme conjugates as do S5a and MBP1. Sun2p (523 amino acids) was found to be homologous to the p58 subunit of the human 26S proteasome. cDNA encoding the p58 component was cloned. Furthermore, expression of a derivative of p58 from which the N-terminal 150 amino acids had been removed restored the function of a null allele of SUN2. During glycerol density gradient centrifugation, both Sunlp and Sun2p comigrated with the known proteasome components. These results, as well as other structural and functional studies, indicate that both Sunlp and Sun2p are components of the regulatory module of the yeast 26S proteasome.

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Section: Discussionmentioning

confidence: 99%

Yeast counterparts of subunits S5a and p58 (S3) of the human 26S proteasome are encoded by two multicopy suppressors of nin1-1.

Kominami

Okura

Kawamura

et al. 1997

MBoC

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“…c-Interferon secreted in inflammatory reactions by CD4 1 and CD8 1 T-cell induces the expression of the so-called inducible forms of b1i, b2i, and b5i replacing the constitutive subunits during de novo synthesis (68), whereas the constitutive forms of b1, b2, and b5 are downregulated (69,70). Since this is a very quick process, many intermediate forms can be observed (71), showing large variation in fragment length produced by the cell during protein degradation.…”

Section: The Proteasomementioning

confidence: 99%

The proteasome and its role in the degradation of oxidized proteins

2008

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SummaryThe generation of free radicals and the resulting oxidative modification of cell structures are omnipresent in mammalian cells. This includes the permanent oxidation of proteins leading to the disruption of the protein structure and an impaired functionality. In consequence, these oxidized proteins have to be removed in order to prevent serious metabolic disturbances. The most important cellular proteolytic system responsible for the removal of oxidized proteins is the proteasomal system. For normal functioning, the proteasomal system needs the coordinated interaction of numerous components. This review describes the fundamental functions of the 20S ''core'' proteasome, its regulators, and the roles of the proteasomal system beyond the removal of oxidized proteins in mammalian cells. IUBMBIUBMB Life, 60(11): 743-752, 2008

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“…Only three of the ␤ subunits (two copies of each) are proteolytically active: ␦ (␤1), X (␤5), and Z (␤5). In cells stimulated by the proinflammatory cytokine IFN-␥, the composition of the proteasome is altered such that the three active ␤ subunits are replaced by inducible subunits: lmp2 (␤1i), lmp7 (␤5i), and mecl1 (␤2i) (12)(13)(14)(15)(16)(17). This modified proteasome is the immunoproteasome (18).…”

Section: Heat Shock Up-regulates Lmp2 and Lmp7 And Enhances Presentatmentioning

confidence: 99%

Heat Shock Up-Regulates lmp2 and lmp7 and Enhances Presentation of Immunoproteasome-Dependent Epitopes

Callahan

Wohlfert

Ménoret

et al. 2006

The Journal of Immunology

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The heat shock response is a canonical regulatory pathway by which cellular stressors such as heat and oxidative stress alter the expression of stress-responsive genes. Some of these stress-responsive genes (heat shock proteins and MHC class I (MHC I)-related chains) play a significant role in the immune system. In this study, we have investigated the impact of stimulating the heat shock response on genes involved in the MHC I presentation pathway. We report that two inducible subunits of the proteasome, lmp2 and lmp7, are transcriptionally up-regulated by heat shock in cells of mouse and human origin. Furthermore, heat-shocked cells show enhanced presentation of the immunoproteasome-dependent MHC I antigenic epitopes NP118–126 of lymphocytic choriomeningitis virus and E1B192–200 of adenovirus, but not immunoproteasome-independent epitopes such as tumor Ag AH1 and SV40 large T Ag epitope II223–231. These findings show a novel immunological sequel to the cellular response to stress that may play a key role during fever or other homeostatic perturbations.

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cDNA Cloning and Interferon γ Down-Regulation of Proteasomal Aubunits X and Y

Cited by 180 publications

References 27 publications

Yeast counterparts of subunits S5a and p58 (S3) of the human 26S proteasome are encoded by two multicopy suppressors of nin1-1.

Yeast counterparts of subunits S5a and p58 (S3) of the human 26S proteasome are encoded by two multicopy suppressors of nin1-1.

The proteasome and its role in the degradation of oxidized proteins

Heat Shock Up-Regulates lmp2 and lmp7 and Enhances Presentation of Immunoproteasome-Dependent Epitopes

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