Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ‐domain motif interaction and identification of putative functional modules

Abstract

Graphical abstract

T2D and Depression Risk Gene Proteasome Modulator 9 is Linked to Insomnia

“…The IL6 receptor has been identified as a novel PSMD9-interacting partner which further supports PSMD9 role in the inflammatory response 39 . In addition, PSMD9 mediates IκBα degradation via PSMD9-PDZ domain-specific interaction and a hnRNPA1 C-terminus motif 40 .…”

“…Therefore, PSMD9 may have a pathogenic role in inflammation and autoimmunity 38 . The 26S proteasome is also a factor regulating ligand-dependent retinoid-target genes transcription, and PSMD9 PDZ interaction domain has a role in mRNA processing and editing, transcriptional regulation, hormone and receptor activity and protein translation 39 . Additionally, novel PSMD9-interacting partners have been recently identified: hnRNPA1 (an RNA binding protein), S14 (a ribosomal protein), CSH1 (a growth hormone), E12 (a transcription factor) and IL6 receptor 39 .…”

“…The 26S proteasome is also a factor regulating ligand-dependent retinoid-target genes transcription, and PSMD9 PDZ interaction domain has a role in mRNA processing and editing, transcriptional regulation, hormone and receptor activity and protein translation 39 . Additionally, novel PSMD9-interacting partners have been recently identified: hnRNPA1 (an RNA binding protein), S14 (a ribosomal protein), CSH1 (a growth hormone), E12 (a transcription factor) and IL6 receptor 39 . This has added to our understanding of the PSMD9 role in regulation of transcription, processing and editing of mRNA, protein translation, hormone and receptor activity 39 .…”

“…Additionally, novel PSMD9-interacting partners have been recently identified: hnRNPA1 (an RNA binding protein), S14 (a ribosomal protein), CSH1 (a growth hormone), E12 (a transcription factor) and IL6 receptor 39 . This has added to our understanding of the PSMD9 role in regulation of transcription, processing and editing of mRNA, protein translation, hormone and receptor activity 39 . Another study demonstrated that PSMD9 inhibits basal and tumor necrosis factor α (TNF-α)-mediated NF-kB activation via inhibition of nuclear factor kB α (IkBα) proteasome degradation 40 .…”

Gene expression in the liver of female, but not male mice treated with rapamycin resembles changes observed under dietary restriction

“…Similar results were found when we measured the gene transcripts for key proteins involved in degradation processes i.e., ubiquitin-proteasome and autophagy pathways. For the ubiquitin-proteasome pathway, we measured mRNA levels for Usp2 (ubiquitin specific peptidase 2), a cysteine protease that cleaves ubiquitin from the poly ubiquitin chains of proteins (Renatus et al, 2006 ; Stevenson et al 2007 ) and Psmd9 , a non-ATPase subunit of the 19S regulatory complex which aids in proteasome assembly and interacts with poly-ubiquitin chains of target proteins, influencing ubiquitination (Sangith et al, 2014 ). As shown in Figure 3 A and B, DR in both genders significantly upregulates expression of both Usp2 and Psmd9 genes when compared to AL mice, an effect that is mimicked in females but not in males fed rapamycin.…”