A Conserved F Box Regulatory Complex Controls Proteasome Activity in Drosophila

Bader, Maya; Benjamin, Sigi; Wapinski, Orly L.; Smith, David M.; Goldberg, Alfred L.; Steller, Hermann

doi:10.1016/j.cell.2011.03.021

Cited by 97 publications

(177 citation statements)

References 53 publications

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“…The PI31 FP domain mediates heterodimerization of SCF Fbxo7 and PI31. Consistent with this fi nding, the fl y homologue DmPI31 was found as a binding partner of the F box protein Nutcracker, a component of a SCF Ub ligase required for caspase activation during sperm differentiation in Drosophila (Bader et al , 2011 ). DmPI31 binds Nutcracker via a conserved mechanism that is also used by mammalian FBXO7 and PI31.…”

Section: Other Proteasome-interacting Proteins (Pips)supporting

confidence: 59%

The proteasome: molecular machinery and pathophysiological roles

Tanaka

Mizushima

Saeki

2012

BCHM

110

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The 26S proteasome, in collaboration with ubiquitin, operates the energy-dependent regulated proteolysis process in eukaryotic cells. Over the past 30 years, several studies have comprehensively characterized the structure and molecular/ physiological functions of the 26S proteasome. It is a sophisticated 2.5-MDa protein degradation machine comprising a proteolytic core particle (CP) and one or two terminal regulatory particle(s) (RP). The CP consists of two outer α rings and two inner β rings, which are made up of seven structurally similar α and β subunits, respectively. The CP contains catalytic threonine residues ( β 1, β 2, and β 5; caspase-like, trypsin-like, and chymotrypsin-like activities, respectively) on the inner surface of the chamber formed by two abutting β rings. Intriguingly, the immunotype proteasomes, named ' immunoproteasome ' and ' thymoproteasome ' , whose catalytic subunits are replaced by the related counterparts, were discovered lately. Both unique isoenzymes essentially contribute to the acquisition of adaptive immunity in vertebrates. The RP, which serves to recognize polyubiquitylated substrate proteins and plays a role in their deubiquitylating, unfolding, and translocation into the interior of the CP for destruction, forms two subcomplexes: the base and the lid. On another front, the PA28 and PA200, alternative CP activator proteins discovered biochemically, both play independent roles in proteolysis of the 26S proteasome. Several studies have highlighted the importance of the proteasome in various intractable diseases that have been increasing in the aged society of the 21st century.

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Section: Other Proteasome-interacting Proteins (Pips)supporting

confidence: 59%

The proteasome: molecular machinery and pathophysiological roles

Tanaka

Mizushima

Saeki

2012

BCHM

110

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“…Recently, Steller's group found that fruit fly PI31, DmPI31, works in cooperation with 26S proteasomes (24,25). They showed that ectopic expression of DmPI31 suppressed an eye phenotype caused by proteasome dysfunction, whereas reducing DmPI31 function enhanced proteasome defects.…”

Section: Discussionmentioning

confidence: 99%

“…There are conflicting reports as to the effect of PI31 on proteasome function. The original paper showed that mammalian PI31 inhibits 20S CP activity in vitro, but other reports indicate that PI31 cooperates with the proteasome in protein degradation in fruit flies (20,(24)(25)(26).…”

Section: Fub1 Is Associated Mainly With the 20s Cpmentioning

confidence: 99%

“…Furthermore, when PI31 was overexpressed in cells, the formation of the immunoproteasome, which is one of the CP subtypes, was attenuated, and thus processing of an immunoproteasome-dependent epitope was impaired (23). In contrast, recent studies have shown that the Drosophila melanogaster PI31 homolog (DmPI31) activated the 26S proteasome in vitro and that knockdown of DmPI31 in flies compromised protein degradation by the proteasome (24,25), while mammalian PI31 had no effect on the in vitro activity of the 26S proteasome (26). In view of these conflicting findings, the physiological role and the mechanism of action of PI31 in proteasome-mediated protein degradation remain enigmatic.…”

mentioning

confidence: 99%

“…Two well-characterized domains exist in PI31 proteins (24,40). The N-terminal FP domain of human and fly PI31 has been shown to bind to the F-box proteins Fbxo7 and Nutcracker (fly homolog of Fbxo7), respectively.…”

Section: Fub1 Is Associated Mainly With the 20s Cpmentioning

confidence: 99%

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N-Terminal α7 Deletion of the Proteasome 20S Core Particle Substitutes for Yeast PI31 Function

Yashiroda

Toda

Otsu

et al. 2015

Molecular and Cellular Biology

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The proteasome core particle (CP) is a conserved protease complex that is formed by the stacking of two outer ␣-rings and two inner ␤-rings. The ␣-ring is a heteroheptameric ring of subunits ␣1 to ␣7 and acts as a gate that restricts entry of substrate proteins into the catalytic cavity formed by the two abutting ␤-rings. The 31-kDa proteasome inhibitor (PI31) was originally identified as a protein that binds to the CP and inhibits CP activity in vitro, but accumulating evidence indicates that PI31 is required for physiological proteasome activity. To clarify the in vivo role of PI31, we examined the Saccharomyces cerevisiae PI31 ortholog Fub1. Fub1 was essential in a situation where the CP assembly chaperone Pba4 was deleted. The lethality of ⌬fub1 ⌬pba4 was suppressed by deletion of the N terminus of ␣7 (␣7⌬N), which led to the partial activation of the CP. However, deletion of the N terminus of ␣3, which activates the CP more efficiently than ␣7⌬N by gate opening, did not suppress ⌬fub1 ⌬pba4 lethality. These results suggest that the ␣7 N terminus has a role in CP activation different from that of the ␣3 N terminus and that the role of Fub1 antagonizes a specific function of the ␣7 N terminus. The 26S proteasome is a multicatalytic protease complex conserved in eukaryotes (1). Its main function is to serve as a selective and regulated mechanism for intracellular protein degradation, mainly in a ubiquitin-dependent manner. The 26S proteasome consists of one 20S core particle (CP) and one or two 19S regulatory particles (RPs) attached to the CP.The CP exerts proteolytic activity and is made up of four axially stacked heteroheptameric rings: two outer ␣-rings formed by ␣1 to ␣7 and two inner ␤-rings formed by ␤1 to ␤7. Of the seven ␤-subunits, only ␤1, ␤2, and ␤5 have proteolytic activities. The archaebacterium Thermoplasma acidophilum has a prototype of the CP that consists of a single type of ␣-and ␤-subunit, with all the ␤-subunits being catalytically active. Another difference between archaeal and eukaryotic CPs is the structure of the ␣-rings. Whereas archaeal CPs have a disordered gate that is permeable to peptide substrates, the eukaryotic ␣-ring of the CP is primarily in a closed state because the N termini of ␣1, ␣2, ␣3 (Pre9), ␣6, and ␣7 project into the opening of the ␣-ring (2-4). Therefore, the activity of the eukaryotic CP is basically latent. Of the ␣-subunits, ␣3 is supposed to be most important because the N terminus of ␣3 projects directly across the pseudo 7-fold symmetry axis. In addition, its deletion (␣3⌬N) causes disorder of the N termini of ␣1, ␣5, and ␣7, leading to an open state of ␣-rings (5). In vivo, binding of CP activators, such as the RPs, opens the closed ␣-ring (6, 7).The CP is assembled with the aid of various proteasome-dedicated chaperones in mammals and Saccharomyces cerevisiae (8-13). The assembly of CPs begins with the formation of the ␣-ring, assisted by the heterodimeric complexes PAC1-PAC2/Pba1-Pba2 and PAC3-PAC4/Pba3-Pba4 in mammals/yeast. After the formation of the ␣-...

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Cell death proteins: An evolutionary role in cellular adaptation before the advent of apoptosis

Dick

Megeney

2013

BioEssays

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Programmed cell death (PCD) or apoptosis is a broadly conserved phenomenon in metazoans, whereby activation of canonical signal pathways induces an ordered dismantling and death of a cell. Paradoxically, the constituent proteins and pathways of PCD (most notably the metacaspase/caspase protease mediated signal pathways) have been demonstrated to retain non-death functions across all phyla including yeast, nematodes, drosophila, and mammals. The ancient conservation of both death and non-death functions of PCD proteins raises an interesting evolutionary conundrum: was the primordial intent of these factors to induce cell death or to regulate other cellular adaptations? Here, we propose the hypothesis that apoptotic behavior of PCD proteins evolved or were co-opted from core non-death functions.

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A Conserved F Box Regulatory Complex Controls Proteasome Activity in Drosophila

Cited by 97 publications

References 53 publications

The proteasome: molecular machinery and pathophysiological roles

The proteasome: molecular machinery and pathophysiological roles

N-Terminal α7 Deletion of the Proteasome 20S Core Particle Substitutes for Yeast PI31 Function

Cell death proteins: An evolutionary role in cellular adaptation before the advent of apoptosis

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