Post-translational processing of a major histocompatibility complex-encoded proteasome subunit, LMP-2

Martinez, Coleen K.; Monaco, John J.

doi:10.1016/0161-5890(93)90136-y

Cited by 14 publications

(7 citation statements)

References 21 publications

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“…Rad23 and Rpn10 can interact with multiubiquitinated proteins (6,28,38) and the proteasome (32), and several recent studies have indicated that they contribute to the degradation of ubiquitinated proteins by the proteasome (6,9,21,24). Loss of both proteins results in temperature-sensitive growth, defects in proteolysis, and a delay in the G 2 phase of the cell cycle (22).…”

mentioning

confidence: 99%

Proteasome-Mediated Degradation of Cotranslationally Damaged Proteins Involves Translation Elongation Factor 1A

Chuang

Chen²,

Lambertson³

et al. 2005

Molecular and Cellular Biology

162

158

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Rad23 and Rpn10 play synergistic roles in the recognition of ubiquitinated proteins by the proteasome, and loss of both proteins causes growth and proteolytic defects. However, the physiological targets of Rad23 and Rpn10 have not been well defined. We report that rad23⌬ rpn10⌬ is unable to grow in the presence of translation inhibitors, and this sensitivity was suppressed by translation elongation factor 1A (eEF1A). This discovery suggested that Rad23 and Rpn10 perform a role in translation quality control. Certain inhibitors increase translation errors during protein synthesis and cause the release of truncated polypeptide chains. This effect can also be mimicked by ATP depletion. We determined that eEF1A interacted with ubiquitinated proteins and the proteasome following ATP depletion. eEF1A interacted with the proteasome subunit Rpt1, and the turnover of nascent damaged proteins was deficient in rpt1. An eEF1A mutant (eEF1A D156N ) that conferred hyperresistance to translation inhibitors was much more effective at eliminating damaged proteins and was detected in proteasomes in untreated cells. We propose that eEF1A is well suited to detect and promote degradation of damaged proteins because of its central role in translation elongation. Our findings provide a mechanistic foundation for defining how cellular proteins are degraded cotranslationally.Rad23 and Rpn10 can interact with multiubiquitinated proteins (6, 28, 38) and the proteasome (32), and several recent studies have indicated that they contribute to the degradation of ubiquitinated proteins by the proteasome (6, 9, 21, 24). Loss of both proteins results in temperature-sensitive growth, defects in proteolysis, and a delay in the G 2 phase of the cell cycle (22). We isolated yeast TEF1, a gene encoding the eukaryotic translation elongation factor 1A (eEF1A) (15), as a dosage suppressor of the cold (13°C) sensitivity of rad23⌬ rpn10⌬ (22). eEF1A promotes translation elongation through the binding and release of aminoacyl tRNAs, in a process that is coupled to GTP hydrolysis (15). In addition to its well-characterized role in translation elongation, in vitro studies showed that eEF1A could bind nascent as well as unfolded peptides and proteins (17,23). eEF1A might possess a chaperone-like activity that prevents the aggregation of nascent polypeptide chains (4), since it could bind an unfolded protein but not a correctly folded counterpart (17). eEF1A could also stimulate the degradation of N␣-acetylated proteins (12). The isolation of eEF1A as a suppressor of rad23⌬ rpn10⌬ suggested that it performs a central role in monitoring the accuracy of protein synthesis. These studies also revealed an important function for Rad23 and Rpn10 in protein synthesis quality control.A significant fraction of newly synthesized proteins is degraded cotranslationally (29,33,35). These nascent damaged proteins can be ubiquitinated while bound to the ribosome (31), demonstrating that there exists a close coupling between the pathways of protein synthesis and protein degrada...

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mentioning

confidence: 99%

Proteasome-Mediated Degradation of Cotranslationally Damaged Proteins Involves Translation Elongation Factor 1A

Chuang

Chen²,

Lambertson³

et al. 2005

Molecular and Cellular Biology

162

158

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“…The mature protein sequence coincides precisely with the start of exon 2, exactly the same as in the closely related Lmp2 gene (Martinez and Monaco 1993).…”

Section: Genomic Delta Coding Sequence From Dba/2jmentioning

confidence: 87%

“…The exons vary in size -E1 >--99 bp, E2 = 68 bp, E3 = 132 bp, E4 = 130 bp, E5 = 145 bp, and E6 = 143 bp, but each intron/ exon boundary is located in exactly the same position relative to the protein sequence as in Lmp2 (Martinez and Monaco 1993). The introns are more heterogeneous in size: I1 = 387 bp, I2 = 397 bp, I3 = 118 bp, I4 = 503 bp, and I5 = 112 bp.…”

Section: Genomic Delta Coding Sequence From Dba/2jmentioning

confidence: 99%

Characterization and mapping of the gene encoding mouse proteasome subunit DELTA (Lmp19)

Woodward

Monaco

1995

Immunogenetics

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The proteasome subunit DELTA is unusually closely related to the major histocompatibility complex (MHC)-linked proteasome subunit, LMP2. The sequence of a mouse cDNA for DELTA confirms that this 22,100 M(r) proteasome subunit is highly conserved across species. Sequence analysis of the mouse gene encoding DELTA, designated Lmp19, indicates that it consists of six exons and five introns, similar to the Lmp2 gene. The 5' upstream region lacks a TATA regulatory sequence, which is also absent from proteasome genes isolated from Drosophila. BXD recombinant inbred (RI) mice were used to map the potential chromosomal location of Lmp19, and revealed that the DELTA subunit has related sequences present on two different mouse chromosomes, chromosomes 1 and 11. Typing of 89 progeny from a C57BL/6J X Mus spretus DNA backcross panel (BSS) confirmed the chromosome 1 assignment. Southern hybridization with a polymerase chain reaction-generated Lmp19 intron 2-specific probe indicates that the Lmp19 genomic clone corresponds to the sequence on chromosome 11, and further suggests that the chromosome 1 copy represents a processed pseudogene (Lmp19-ps1).

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“…At least two chromatographically distinct proteasome subsets (A and B) from P388D1 cells have been iden tified that are similar to serologically defined LMP2+ and LMP2~ proteasomes identified previously [17]. However, both HIC protea some subsets (A and B) lack the unprocessed form [28] of the LMP2 subunit, LMP 10, LMP 12 and proteasome polypeptide 3P that are characteristic of P388D1 protesome immunoprecipitates [16,17] (fig, 5). Recent data demonstrate that LMP 12 is in fact the precur sor of LMP7 [Nandi and Monaco, unpub lished], and that the unprocessed forms of LMP2 and LMP7 are incorporated into a proteolytically inactive proteasome precursor [6].…”

Section: Discussionmentioning

confidence: 97%

“…Thus, distinct proteasome subsets have been separated by HIC, and we have designated these subset A and subset B. Surprisingly, both subsets A and B lack LMP subunits LMP10, LMP 12 and unprocessed LMP2 [28], as well as proteasome polypeptide 3P that are characteristic of H-2d LMP and pro teasome immunoprecipitates [17], although these subunits were present in an anti-proteasome immunoprecipitate obtained from re duced in comparison to peak-A proteasomes, similar to LMP2" proteasomes [17]. Likewise, proteasome polypeptide IP is significantly in creased in peak-B proteasomes in comparison to peak-A proteasomes.…”

Section: Characterization Of Purified Proteasome Subsetsmentioning

confidence: 99%

Biochemical Purification of Distinct Proteasome Subsets

Brown

Monaco²

1993

Enzyme Protein

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Proteasomes are intricate cellular proteases that are able to degrade many protein and peptide substrates in vitro. These particles are structurally complex; they are assembled from at least 14 small molecular mass polypeptide subunits to form mature 20S proteasomes. Recently, we demonstrated that proteasome subsets may be discriminated by serological criteria, and have found that subtle differences in the subunit composition of proteasomes can alter their cleavage specificity. Proteasome structural complexity is further enhanced when some proteasomes associate with additional proteins to form a 26S ATPand ubiquitin-dependent protease. Herein we confirm the existence of distinct cellular forms of proteasomes, and show that they differ in their hydrophobic characteristics. We have reproducibly purified, using solely biochemical techniques, distinct proteasome subsets similar to the serologically defined LMP2^+ and LMP2^- proteasomes. These proteasome subsets differ in their expression of at least three polypeptides, and both lack several additional polypeptides as compared to the serologically defined LMP2^+ and LMP2^- proteasomes. Finally, we demonstrate that these structurally unique proteasomes differ in their capacity to cleave a defined panel of fluorogenic peptide substrates. It appears that mammalian cells might recruit and modify proteasomes to perform distinct cellular tasks.

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Post-translational processing of a major histocompatibility complex-encoded proteasome subunit, LMP-2

Cited by 14 publications

References 21 publications

Proteasome-Mediated Degradation of Cotranslationally Damaged Proteins Involves Translation Elongation Factor 1A

Proteasome-Mediated Degradation of Cotranslationally Damaged Proteins Involves Translation Elongation Factor 1A

Characterization and mapping of the gene encoding mouse proteasome subunit DELTA (Lmp19)

Biochemical Purification of Distinct Proteasome Subsets

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