The Ubiquitin System

Hershko, Avram; Ciechanover, Aaron

doi:10.1146/annurev.biochem.67.1.425

Cited by 7,729 publications

(5,439 citation statements)

References 302 publications

(323 reference statements)

Supporting

Mentioning

5,338

Contrasting

Unclassified

Order By: Relevance

“…At least four ubiquitin molecules, conserved peptides of 76 amino acids, are required for a poly-ubiquitin chain to be recognized by the proteasome. Hershko and colleagues in the early 1980s showed that poly-ubiquitylation requires three ATP-dependent enzymes: the ubiquitin activation enzyme (E1), a family of ubiquitin conjugating enzymes (E2) and a family of ubiquitin protein ligases (E3) ( Hershko & Ciechanover, 1998). First, ATP hydrolysis is required to activate the AMP linkage to the C-terminal glycine of ubiquitin which enables the transfer of the ubiquitin moiety to the active site cysteine of the E1.…”

Section: Discussion/analysis Of the Literaturementioning

confidence: 99%

“…In eukaryotic cells two highly conserved degradation pathways exist: long-lived proteins are degraded within the lysosome, an organelle with membranes which protect the surrounding cytoplasm against lysosomal hydrolases ( Rendueles & Wolf, 1988); short-lived proteins are degraded by proteasomes, multimeric protease complexes which move between the nucleo- and cytoplasm ( Hershko & Ciechanover, 1998). Proteasomal substrates are often nuclear proteins such as proteins regulating cell cycle progression (cyclin-dependant kinases and their inhibitors), gene expression (transcriptions factors), DNA damage and stress response; although, misfolded proteins occurring during protein synthesis in the cytoplasm are also rapidly degraded by the proteasome ( Kirschner, 1999; Vabulas & Hartl, 2005; von Mikecz, 2006).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Intracellular Dynamics of the Ubiquitin-Proteasome-System

Chowdhury

Enenkel

2015

F1000Res

View full text Add to dashboard Cite

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.

show abstract

Section: Discussion/analysis Of the Literaturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intracellular Dynamics of the Ubiquitin-Proteasome-System

Chowdhury

Enenkel

2015

F1000Res

View full text Add to dashboard Cite

show abstract

“…Ubiqutination recruits a catalytic reaction to ubiquitinate the substrate 1. Three ubiquitin enzymes, E1 ubiquitin activating, E2 ubiquitin conjugating, and E3 ubiquitin ligase are sequentially recruited in this cascade reaction 2, 3, 4.…”

Section: Introductionmentioning

confidence: 99%

E3 Ubiquitin ligase RNF126 regulates the progression of tongue cancer

Wang

Zhao

et al. 2016

Cancer Medicine

View full text Add to dashboard Cite

This study aims to analyze the role of RNF126 in the oncogenesis of tongue cancer. The cell proliferation and viability of human tongue cancer cells, SCC25 and SCC9 cells, were determined by cell counting and MTT assay, respectively. The effect of RNF126 on regulating AKT signaling pathway was analyzed through western blotting. The transplantation tumor model of nude mice was used to evaluate the tumorigenecity of RNF126. Knockdown of RNF126 inhibited the proliferation and viability of SCC9 and SCC25 cells. Inhibition of RNF126 also decreased the activity of AKT1 as well as its downstream molecules. Furthermore, RNF126 regulated the tumor volume on mice model. These data suggested that RNF126 might be related to the progression of tongue cancer through regulating AKT signaling pathway.

show abstract

“…One major pathway is the regulation of protein amount through ubiquitin-dependent proteolysis (Pagano, 1997;Hershko, 1997;Hershko and Chiechanover, 1998;Almond and Cohen, 2002). The ubiquitin-dependent proteolysis system requires a set of enzymes as follows: ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2) and ubiquitin ligase (E3).…”

Section: Introductionmentioning

confidence: 99%

Tumor suppressor candidate TSSC5 is regulated by UbcH6 and a novel ubiquitin ligase RING105

Yamada

Gorbsky

2005

Oncogene

View full text Add to dashboard Cite

The region of human chromosome 11p15.5 is linked with Beckwith-Wiedemann syndrome that is associated with susceptibility to Wilms' tumor, rhabdomyosarcoma and hepatoblastoma. TSSC5 (tumor-suppressing subchromosomal transferable fragment cDNA; also known as ORCTL2/IMPT1/BWR1A/SLC22A1L) is located in the region. The expression of TSSC5 and other genes in the region is regulated through paternal imprinting. Mutations and/or reduced expression of TSSC5 have been found in certain tumors. TSSC5 encodes an efflux transporter-like protein with 10 transmembrane domains, whose regulation may affect drug sensitivity, cellular metabolism and growth. Here, we present evidences indicating that RING105, a novel conserved RING-finger protein with a PA (protease-associated) domain and a PEST sequence, is a ubiquitin ligase for TSSC5 that can function in concert with the ubiquitin-conjugating enzyme UbcH6. The polyubiquitin target site on TSSC5 was mapped to a region in the 6th hydrophilic loop. Ectopic expression of RING105 in HeLa cells caused an accumulation of cells during G1 that was not observed with the expression of a form of RING105 in which a residue within the RING finger was mutated to inactivate its ligase activity. UbcH6-RING105 may define a novel ubiquitin-proteasome pathway that targets TSSC5 in mammalian cells.

show abstract

The Ubiquitin System

Cited by 7,729 publications

References 302 publications

Intracellular Dynamics of the Ubiquitin-Proteasome-System

Intracellular Dynamics of the Ubiquitin-Proteasome-System

E3 Ubiquitin ligase RNF126 regulates the progression of tongue cancer

Tumor suppressor candidate TSSC5 is regulated by UbcH6 and a novel ubiquitin ligase RING105

Contact Info

Product

Resources

About