Multifaceted functions of RPS27a: An unconventional ribosomal protein

Luo, Jingshun; Zhao, Hong; Chen, Linxi; Liu, Meiqing

doi:10.1002/jcp.30941

Cited by 24 publications

(14 citation statements)

References 109 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RPS27A, a component of the ribosome, participates in the regulation of protein synthesis [31,32]. Firstly, RPS27A participates in the recognition and initiation of mitophagy signals.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Integrated bioinformatics identify the critical genes of mitophagy in myocardial ischemia- reperfusion injury

Chen,

Liu,

Yuan

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Myocardial ischemia is a prevalent cardiovascular disease with a high incidence and mortality rate. Restoring blood flow to the ischemic myocardium as soon as possible is crucial for improving patients' prognosis, but this process can lead to myocardial ischemia-reperfusion injury (MIRI). Mitophagy is a specific cellular autophagic process that has been consistently linked to various cardiovascular disorders.Nevertheless, the connection between ischemia-reperfusion and mitophagy remains unclear. This study's objective is to discern and substantiate central mitophagy-related genes associated with MIRI through bioinformatics analysis. Methods: The microarray expression profile dataset (GSE108940) was obtained from the Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were identified using GEO2R. These DEGs were then cross-referenced with genes in the mitophagy database. Differential nucleotide sequence analysis used enrichment analysis.The DEGs were obtained through protein-protein interaction (PPI)network analysis. And the hub genes were clustered by cytoHubba and MCODE of Cytoscape software. GSEA analysis was conducted on central genes. Finally, we conducted Western blotting, immunofluorescence, and quantitative polymerase chain reaction (qPCR) analyses to corroborate the expression patterns of pivotal genes in MIRI-afflicted rats. Results: 2719 DEGs and 61 mitophagy-DEGs were obtained,followed by enrichment analyses and construction of PPI network. HSP90AA1, RPS27A, EEF2, EIF4A1, EIF2S1,HIF-1α and BNIP3 were the 7 hub genes identified by cytoHubba and MCODE of Cytoscape software. The functional clustering score of HIF-1α and BNIP3 was 9.647 by analysis of Cytoscape (MCODE). In our constructed MIRI rat model, western blot and immunofluorescence confirmed a significant elevation in the expression of HIF-1α and BNIP3, along with a significant increase in the ratio of LC3II to LC3I. Finally,qPCR confirmed that expression of HIF-1α, BNIP3 and LC3 mRNA in MIRI group was elevated significantly. Conclusions: Seven central genes among the mitophagy-related DEGs have been pinpointed, potentially holding pivotal significance in MIRI, which indicated that HIF-1α/BNIP3 pathway of mitophag was correlated with pathogenesis of MIRI. Mitophagy may play an important role in MIRI.This research will offer valuable insights into the underlying mechanisms and potential therapeutic targets, which can be explored in future studies.

show abstract

“…RPS27A, a component of the ribosome, participates in the regulation of protein synthesis [31,32]. Firstly, RPS27A participates in the recognition and initiation of mitophagy signals.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Integrated bioinformatics identify the critical genes of mitophagy in myocardial ischemia- reperfusion injury

Chen,

Liu,

Yuan

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…As temperatures increased, there were modifications to protein synthesis and turnover processes (pathway: protein catabolic process, protein ubiquitination, protein polyubiquitination; hub transcripts: rps27a , cops5 , hap1 , rnf8 , usp13 , fbxo45 , smurf2 , rplp0 , bop1 , eif3d ) key to translation, ubiquitination and amino acid recycling. Interestingly, rps27a , with dual roles providing both ubiquitin and ribosome structural components (Klinge et al, 2012; Luo et al, 2022), was at the centre of the network with the largest number of protein–protein interactions and betweenness score, emphasizing its role within the regulatory network in response to thermal stress. These protein synthesis and recycling mechanisms are key to modifying the organism's existing phenotype as environments shift, and without their proper function may leave the organism vulnerable to the effects of compounding stressors (Davies et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Elevated temperatures reduce population‐specific transcriptional plasticity in developing lake sturgeon (Acipenser fulvescens)

et al. 2023

View full text Add to dashboard Cite

Rising mean and variance in temperatures elevates threats to endangered freshwater species such as lake sturgeon, Acipenser fulvescens. Previous research demonstrated that higher temperatures during development result in physiological consequences for lake sturgeon populations throughout Manitoba, Canada, with alteration of metabolic rate, thermal tolerance, transcriptional responses, growth and mortality. We acclimated lake sturgeon (30-60 days post fertilization, a period of high mortality) from northern and southern populations (56°02′46.5″N, 96°54′18.6″W and 50°17′52″N, 95°32′51″W, respectively, separated by approximately 650 km) within Manitoba to current (summer highs of 20-23°C) and future projected (+2-3°C) environmental temperatures of 16, 20 and 24°C for 30 days, and we measured gill transcriptional responses using RNAseq. Transcripts revealed SNPs consistent with genetically distinct populations and transcriptional responses altered by acclimation temperature. There were a higher number of differentially expressed transcripts observed in the southern, compared to the northern, population as temperatures increased, indicating enhanced transcriptional plasticity. Both lake sturgeon populations responded to elevated acclimation temperatures by downregulating the transcription of genes involved in protein synthesis and energy production. Furthermore, there were population-specific thresholds for the downregulation of processes promoting transcriptional plasticity as well as mitochondrial function as the northern population showed decreases at 20°C, while this capacity was not diminished until 24°C in the southern population. These transcriptional responses highlight the molecular impacts of increasing temperatures for divergent lake sturgeon populations during vulnerable developmental periods and the critical influence of transcriptome plasticity on acclimation capacity.

show abstract

“…Another interesting hit was also RPS27A, the ubiquitin and ribosomal protein S27A gene, that expresses a fusion protein between RPS27A and ubiquitin. RPS27A is one of the cellular sources of ubiquitin expression, together with UBB (P-Val log10(-1.2)), UBC (P-Val log10(-0.6)) and UBA52 (P-Val log10(-2.1 (Luo et al, 2022;Redman & Rechsteiner, 1989). Based on this data and the redundant nature of the cellular ubiquitin sources we hypothesize that in these HEK293 cells RPS27A is the main source of ubiquitin expression.…”

Section: Generation and Chemical And In-depth Genetic Validation Of A...mentioning

confidence: 75%

Reinstating targeted protein degradation with DCAF1 PROTACs in CRBN PROTAC resistant settings

Schröder

Renatus

Liang

et al. 2023

Preprint

View full text Add to dashboard Cite

Targeted protein degradation (TPD) of neo-substrates with proteolysis targeting chimeras (PROTACs) or molecular glues has emerged as a key modality in exploring new biology as well as designing new drug candidates where catalytic inhibition is neither efficacious nor an option. TPD is mediated through harnessing E3 ligases and redirecting them to ubiquitinate de novo target proteins for subsequent proteasomal degradation. Until recently, E3 ligase chemical matter available for mediating TPD has been limited to a relatively low number of ligases, considering that over 600 E3 ligases are encoded by the human genome. In addition, the most utilized ligase for TPD approaches, CRBN, has been observed to be downregulated in settings of acquired resistance to immunomodulatory inhibitory drugs (IMiDs). IMiDs are molecular glues that target IKZF transcription factors to CRBN for degradation. Resistance is potentially accelerated by non-essentiality of CRBN for cell viability. Here we investigated if the essential E3 ligase receptor DCAF1 can be harnessed for TPD utilizing a potent, non-covalent DCAF1 binder. We show that this binder, selective for the CRL4DCAF1 E3 ligase complex, can be functionalized into an efficient DCAF1-BRD9 PROTAC. Chemical and genetic rescue experiments confirm specific degradation via the CRL4DCAF1 E3 ligase. We further highlight the versatility of DCAF1 for TPD by developing a DCAF1-dasatininb PROTAC targeting multiple cytosolic and membrane bound tyrosine kinases. We expand these findings towards Brutons tyrosine kinase (BTK) selective PROTACs and through extensive optimization and characterization efforts share key observations that led to a potent and selective DCAF1-BTK PROTAC (DBt-10). Finally, with this PROTAC DBt-10, we show rescue of BTK degradation in a BTK-dependent, CRBN-degradation-resistant cell line and provide a rationale for E3 ligase swap to overcome CRBN mediated resistance.

show abstract

Multifaceted functions of RPS27a: An unconventional ribosomal protein

Cited by 24 publications

References 109 publications

WITHDRAWN: Integrated bioinformatics identify the critical genes of mitophagy in myocardial ischemia- reperfusion injury

WITHDRAWN: Integrated bioinformatics identify the critical genes of mitophagy in myocardial ischemia- reperfusion injury

Elevated temperatures reduce population‐specific transcriptional plasticity in developing lake sturgeon (Acipenser fulvescens)

Reinstating targeted protein degradation with DCAF1 PROTACs in CRBN PROTAC resistant settings

Contact Info

Product

Resources

About