ATP-dependent incorporation of 20S protease into the 26S complex that degrades proteins conjugated to ubiquitin.

Eytan, Esther; Ganoth, Dvora; Armon, Tamar; Hershko, Avram

doi:10.1073/pnas.86.20.7751

Cited by 362 publications

(224 citation statements)

References 35 publications

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“…On the other hand, the 30 kDa ubiquitin C-terminal hydrolase (a member of UCH family 1) was devoid of such specificity [1], in agreement with earlier reports [2,3]. Because several isopeptidases and ubiquitin C-terminal hydrolases have been described [4,5,6,7], the cDNA cloning of one partially defined 100 kDa de-ubiquitinase offers the opportunity to (i) clarify the structure/function relationship, (ii) possibly unravel a member of new class of ubiquitin specific proteinases, and (iii) to express the protein in amounts sufficient for extensive biochemical characterization and possible biotechnological usage. To this end, partial NH2-terminal sequence determination of peptides derived from the enzyme isolated from human erythrocytes, was carried out.…”

Section: Introductionsupporting

confidence: 88%

cDNA cloning of a human 100 kDa de‐ubiquitinating enzyme: the 100 kDa human de‐ubiquitinase belongs to the ubiquitin C‐terminal hydrolase family 2 (UCH2)

et al. 1995

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The full length cDNA encoding a 100 kDa human de-ubiquitinating enzyme, referred to as de-ubiqnitinase was obtained using one clone selected from a randomly sequenced human brain cDNA library and specific primers. The sequence of 18 peptides generated from the de-ubiquitinase isolated from outdated human erythrocytes matched perfectly with the predicted amino acid sequence, which would encode a protein containing 858 amino acids (calculated M r = 95,743 Da). Homology search disclosed that the protein is a member of a large family of ubiquitin C-terminal hydrolases (UCH2), that was defined on the basis of the presence of two specific patterns, 'the Cys-and His-domains', which are likely to be involved in the de-ubiquitinating activity [7]. An additional conserved region, 'the aspartic acid domain', was also identified, the functional role of which is unknown.

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Section: Introductionsupporting

confidence: 88%

cDNA cloning of a human 100 kDa de‐ubiquitinating enzyme: the 100 kDa human de‐ubiquitinase belongs to the ubiquitin C‐terminal hydrolase family 2 (UCH2)

et al. 1995

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“…Proteasome holo-enzymes engaged in the degradation of poly-ubiquitylated proteins require the RP, thus occur either as RP-CP or RP-CP-RP, also termed the 26S and the 30S proteasome, respectively ( Eytan et al , 1989). …”

Section: Discussion/analysis Of the Literaturementioning

confidence: 99%

Intracellular Dynamics of the Ubiquitin-Proteasome-System

Chowdhury

Enenkel

2015

F1000Res

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The ubiquitin-proteasome system is the major degradation pathway for short-lived proteins in eukaryotic cells. Targets of the ubiquitin-proteasome-system are proteins regulating a broad range of cellular processes including cell cycle progression, gene expression, the quality control of proteostasis and the response to geno- and proteotoxic stress. Prior to degradation, the proteasomal substrate is marked with a poly-ubiquitin chain. The key protease of the ubiquitin system is the proteasome. In dividing cells, proteasomes exist as holo-enzymes composed of regulatory and core particles. The regulatory complex confers ubiquitin-recognition and ATP dependence on proteasomal protein degradation. The catalytic sites are located in the proteasome core particle. Proteasome holo-enzymes are predominantly nuclear suggesting a major requirement for proteasomal proteolysis in the nucleus. In cell cycle arrested mammalian or quiescent yeast cells, proteasomes deplete from the nucleus and accumulate in granules at the nuclear envelope (NE) / endoplasmic reticulum (ER) membranes. In prolonged quiescence, proteasome granules drop off the NE / ER membranes and migrate as stable organelles throughout the cytoplasm, as thoroughly investigated in yeast. When quiescence yeast cells are allowed to resume growth, proteasome granules clear and proteasomes are rapidly imported into the nucleus.Here, we summarize our knowledge about the enigmatic structure of proteasome storage granules and the trafficking of proteasomes and their substrates between the cyto- and nucleoplasm.Most of our current knowledge is based on studies in yeast. Their translation to mammalian cells promises to provide keen insight into protein degradation in non-dividing cells which comprise the majority of our body’s cells.

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“…The proteasome localizes to the cytoplasm and nucleus of all eukaryotic cells. The 20S proteasome, via an ATP-dependent pathway, associates with other subunits to form a 26S proteasomal complex that can hydrolyze ubiquitinylated proteins (Eytan et al, 1989). Ubiquitinylation itself is a complexly regulated process.…”

Section: Introductionmentioning

confidence: 99%

Prostate carcinoma cell death resulting from inhibition of proteasome activity is independent of functional Bcl-2 and p53

et al. 1998

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ATP-dependent incorporation of 20S protease into the 26S complex that degrades proteins conjugated to ubiquitin.

Cited by 362 publications

References 35 publications

cDNA cloning of a human 100 kDa de‐ubiquitinating enzyme: the 100 kDa human de‐ubiquitinase belongs to the ubiquitin C‐terminal hydrolase family 2 (UCH2)

cDNA cloning of a human 100 kDa de‐ubiquitinating enzyme: the 100 kDa human de‐ubiquitinase belongs to the ubiquitin C‐terminal hydrolase family 2 (UCH2)

Intracellular Dynamics of the Ubiquitin-Proteasome-System

Prostate carcinoma cell death resulting from inhibition of proteasome activity is independent of functional Bcl-2 and p53

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