Thioredoxin Txnl1/TRP32 Is a Redox-active Cofactor of the 26 S Proteasome

Andersen, Karen; Madsen, Lone Galmstrup; Prag, Søren; Johnsen, Anders H.; Semple, Colin A.; Hendil, Klavs B.; Hartmann‐Petersen, Rasmus

doi:10.1074/jbc.m900016200

Cited by 71 publications

(67 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown that Txnl1 binds to Rpn11 and targets eEF1A1 in vivo (86), thus linking protein reduction and degradation pathways. eEF1A1, a known PIP, is thought to specifically interact with Rpt1 (87), and is involved in transferring misfolded nascent proteins from the ribosome to the 26S proteasome for degradation (87).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Dynamic UbR-Proteasome Subcomplexes by In vivo Cross-linking (X) Assisted Bimolecular Tandem Affinity Purification (XBAP) and Label-free Quantitation

Yang

Wang

et al. 2016

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Proteasomes are protein degradation machines that exist in cells as heterogeneous and dynamic populations. A group of proteins function as ubiquitin receptors (UbRs) that can recognize and deliver ubiquitinated substrates to proteasome complexes for degradation. Defining composition of proteasome complexes engaged with UbRs is critical to understand proteasome function. However, because of the dynamic nature of UbR interactions with the proteasome, it remains technically challenging to capture and isolate UbR-proteasome subcomplexes using conventional purification strategies. As a result, distinguishing the molecular differences among these subcomplexes remains elusive. We have developed a novel affinity purification strategy, in vivo cross-linking (X) assisted bimolecular tandem affinity purification strategy (XBAP), to effectively isolate dynamic UbR-proteasome subcomplexes and define their subunit compositions using label-free quantitative mass spectrometry. In this work, we have analyzed seven distinctive UbR-proteasome complexes and found that all of them contain the same type of the 26S holocomplex. However, selected UbRs interact with a group of proteasome interacting proteins that may link each UbR to specific cellular pathways. The compositional similarities and differences among the seven UbRproteasome subcomplexes have provided new insights on functional entities of proteasomal degradation machineries. The strategy described here represents a gen- Proteasomes are multisubunit protein complexes that are responsible for the degradation of ubiquitinated substrates to maintain cell viability and homeostasis. The 26S proteasome is composed of at least 33 subunits (1-3), which can be divided into two subcomplexes: the 20S catalytic core particle (CP) 1 and the 19S regulatory particle (RP). The 20S CP is responsible for various proteolytic activities, and has a highly conserved "barrel"-like structure consisting of two copies each of 14 nonidentical subunits (␣1-7, ␤1-7), which are arranged into four heptameric rings stacked in the order of ␣ 7 ␤ 7 ␤ 7 ␣ 7 (4, 5). The 19S RP intimately interacts with the 20S CP, regulating its activity. In addition, the 19S RP carries diverse functions including substrate recognition and deubiquitination, protein unfolding, and substrate translocation to the 20S CP for degradation (2, 3, 6 -8). In contrast to the highly ordered and stable structure of the 20S CP, the 19S RP appears to be much more flexible and dynamic (3, 9 -11). Current structural analyses have revealed that six Rpt subunits of the 19S RP form a hexameric AAA-ATPase ring to associate with the cylinder ends of the 20S CP, and are surrounded by a shell of Rpn subunits (9 -11). Apart from the

show abstract

Section: Discussionmentioning

confidence: 99%

Characterization of Dynamic UbR-Proteasome Subcomplexes by In vivo Cross-linking (X) Assisted Bimolecular Tandem Affinity Purification (XBAP) and Label-free Quantitation

Yang

Wang

et al. 2016

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

show abstract

“…was decreased in necrotic colonic tissue may reflect a reduced metabolic rate (19) and may lead to reduced protection against glucose deprivation-induced cytotoxicity and lowered protein reduction and proteolysis (20). On the other hand, colonic peroxiredoxin 1 was upregulated, thus increasing the cellular protection against reactive oxygen species damage (21,22).…”

Section: Articlesmentioning

confidence: 99%

Intestinal proteome changes during infant necrotizing enterocolitis

et al. 2012

View full text Add to dashboard Cite

Background: changes in the intestinal and colonic proteome in patients with necrotizing enterocolitis (Nec) may help to characterize the disease pathology and identify new biomarkers and treatment targets for Nec. Methods: Using gel-based proteomics, proteins in Necaffected intestinal and colonic sections were compared with those in adjacent, near-normal tissue sections within the same patients. Western blot and immunohistochemistry were applied to crossvalidate proteomic data and histological location of some selected proteins. results: Thirty proteins were identified with differential expression between necrotic and vital small-intestine sections and 23 proteins were identified for colon sections. Five proteins were similarly affected in the small intestine and colon: histamine receptors (hRs), actins, globins, immunoglobulin, and antitrypsin. Two heat shock proteins (hsPs) were affected in the small intestine. Furthermore, proteins involved in antioxidation, angiogenesis, cytoskeleton formation, and metabolism were affected. Finally, secretory proteins such as antitrypsin, fatty-acid binding protein 5, and haptoglobin differed between Nec-affected and vital tissues. conclusion: Nec progression affects different pathways in the small intestine and colon. hsPs may play an important role, especially in the small intestine. The identified secretory proteins should be investigated as possible circulating markers of Nec progression in different gut regions.

show abstract

“…Thioredoxin-like protein 1 (Txnl1) is an intriguing protein, described to be negatively regulated by glucose deprivation (23) and to act as a redox sensor of endocytosis (24). Its C-terminal domain has been found to bind the regulatory particle of the proteasome (25)(26)(27)(28), whereas the N-terminal domain contains a CXXC motif (25,26). Elongation factor 1-␣1, a protein involved in protein synthesis and also degradation, was identified as a target of Txnl1 in HEK 293 cells (25), but other targets are unknown.…”

mentioning

confidence: 99%