The Proteasome Activators Blm10/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin

Aladdin, Azzam; Yao, Yanhua; Yang, Ciyu; Kahlert, Günther; Ghani, Marvi; Király, Nikolett; Boratkó, Anita; Uray, Karen; Dittmar, Gunnar; Tar, Krisztina

doi:10.3390/biom10111581

Cited by 12 publications

(16 citation statements)

References 74 publications

(113 reference statements)

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“…Unlike PA28αβ and PA28γ, PA200 reduced the ability of 20S proteasomes to degrade oxidized proteins [150]. The PA200-proteasome also mediates the ATP-and ubiquitin-independent degradation of some unstructured substrates and acetylated histones [158][159][160].…”

Section: Role Of the Regulators In The Atp-and Ubiquitin-independent Protein Degradationmentioning

confidence: 99%

Functional Differences between Proteasome Subtypes

Habib

Lesenfants

Vigneron

et al. 2022

Cells

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Four proteasome subtypes are commonly present in mammalian tissues: standard proteasomes, which contain the standard catalytic subunits β1, β2 and β5; immunoproteasomes containing the immuno-subunits β1i, β2i and β5i; and two intermediate proteasomes, containing a mix of standard and immuno-subunits. Recent studies revealed the expression of two tissue-specific proteasome subtypes in cortical thymic epithelial cells and in testes: thymoproteasomes and spermatoproteasomes. In this review, we describe the mechanisms that enable the ATP- and ubiquitin-dependent as well as the ATP- and ubiquitin-independent degradation of proteins by the proteasome. We focus on understanding the role of the different proteasome subtypes in maintaining protein homeostasis in normal physiological conditions through the ATP- and ubiquitin-dependent degradation of proteins. Additionally, we discuss the role of each proteasome subtype in the ATP- and ubiquitin-independent degradation of disordered proteins. We also discuss the role of the proteasome in the generation of peptides presented by MHC class I molecules and the implication of having different proteasome subtypes for the peptide repertoire presented at the cell surface. Finally, we discuss the role of the immunoproteasome in immune cells and its modulation as a potential therapy for autoimmune diseases.

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Section: Role Of the Regulators In The Atp-and Ubiquitin-independent Protein Degradationmentioning

confidence: 99%

Functional Differences between Proteasome Subtypes

Habib

Lesenfants

Vigneron

et al. 2022

Cells

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“…Among the activators, the 19S complex is the most common one, which leads to the formation of the 26S (single-cap) or 30S (double-cap) complexes. More details on the structure and functions of PA200 and PA28 are provided by two articles in this Special Issue [ 2 , 3 ]. The 26S proteasome is the endpoint for proteins marked by the ubiquitin enzyme cascade for degradation and leads to their destruction into peptides and amino acids [ 4 , 5 ].…”

Section: A Macromolecular Degradation Machinementioning

confidence: 99%

Analysis of the Dynamic Proteasome Structure by Cross-Linking Mass Spectrometry

Mendes

Dittmar

2021

Biomolecules

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The 26S proteasome is a macromolecular complex that degrades proteins maintaining cell homeostasis; thus, determining its structure is a priority to understand its function. Although the 20S proteasome’s structure has been known for some years, the highly dynamic nature of the 19S regulatory particle has presented a challenge to structural biologists. Advances in cryo-electron microscopy (cryo-EM) made it possible to determine the structure of the 19S regulatory particle and showed at least seven different conformational states of the proteasome. However, there are still many questions to be answered. Cross-linking mass spectrometry (CLMS) is now routinely used in integrative structural biology studies, and it promises to take integrative structural biology to the next level, answering some of these questions.

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“…The α-rings consist of seven α-subunits each, which form a kind of gate and restrict the access of polypeptides to the catalytic chamber unless regulatory complexes are bound to the CP [ 4 ]. Three classes of PAs were identified in eukaryotes: the ATP-independent Blm10/PA200 [ 5 ], 11S/PA28/PA26 (not present in yeast) [ 6 , 7 ], and the ATP-dependent 19S/PA700/RP activators [ 4 , 8 , 9 ], all of which inserted their C terminus into α-subunit pockets to enable substrate access in the similar manner [ 4 , 10 , 11 ]. The two ends of the barrel-shaped 20S proteasome can bind either the same or different regulatory particles forming homogeneous or hybrid proteasomes, respectively [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

PKR Protects the Major Catalytic Subunit of PKA Cpk1 from FgBlm10-Mediated Proteasome Degradation in Fusarium graminearum

Sun

Zhang

2022

IJMS

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For optimal proteolytic function, the proteasome core (CP or 20S) must associate with activators. The cAMP-PKA pathway is reported to affect the activity of the proteasome in humans. However, the relationship between the proteasome and PKA is not well characterized. Our results showed that the major catalytic subunit Cpk1 was degraded without the protection of Pkr. Eleven (out of 67) pkr suppressors had FgBlm10 C-terminal truncation, one suppressor had an amino acid change mutation in the PRE6 ortholog (FGRRES_07282), and one in the PRE5 ortholog (FGRRES_05222). These mutations rescued the defects in growth and conidial morphology, Cpk1 stability, and PKA activities in the pkr mutant. The interaction of FgBlm10 with FgPre5 and FgPre6 were detected by co-immunoprecipitation, and the essential elements for their interaction were characterized, including the FgBlm10 C-terminus, amino acid D82 of FgPre6 and K62 of FgPre5. Additional FgBlm10-interacting proteins were identified in the wild type and pkr mutant, suggesting that PKA regulates the preference of FgBlm10-mediated proteasome assembly. In addition, PKA indirectly affected the phosphorylation of FgBlm10, and its localization in the nucleus. The truncation of the FgBlm10 C terminus also enhanced nuclear import and bleomycin resistance, suggesting its role in proteasome assembly at DNA damage sites. Collectively, our data demonstrated that regulation between PKA and proteasome degradation is critical for the vegetative growth of F. graminearum.

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The Proteasome Activators Blm10/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin

Cited by 12 publications

References 74 publications

Functional Differences between Proteasome Subtypes

Functional Differences between Proteasome Subtypes

Analysis of the Dynamic Proteasome Structure by Cross-Linking Mass Spectrometry

PKR Protects the Major Catalytic Subunit of PKA Cpk1 from FgBlm10-Mediated Proteasome Degradation in Fusarium graminearum

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