The Cul4‐DDB1‐WDR3/WDR6 Complex Binds SPAK and OSR1 Kinases in a Phosphorylation‐Dependent Manner

Dhiani, Binar Asrining; Mehellou, Youcef

doi:10.1002/cbic.201900454

Cited by 13 publications

(12 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…WDR3 regulates proteins characterized by the presence of several WD motifs (also known as the Trp-Asp or WD40 motifs). These proteins are involved in cell cycle progression, signal transduction and apoptosis ( Dhiani & Mehellou, 2020 ; McMahon et al, 2010 ; Liu et al, 2011 ). UTP12 is the homolog of WDR3 in yeast, and it is a part of the pre-rRNA processing complex that is essential for rRNA processing and synthesis of the small ribosomal subunit ( Dragon et al, 2002 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis for the identification of hub genes and signaling pathways related to circANRIL

Qin

Zheng

et al. 2022

PeerJ

View full text Add to dashboard Cite

Background Antisense noncoding RNA in the INK4 locus (ANRIL) is located on human chromosome 9p21, and modulation of ANRIL expression mediates susceptibility to some important human disease, including atherosclerosis (AS) and tumors, by affecting the cell cycle circANRIL and linear ANRIL are isoforms of ANRIL. However, it remains unclear whether these isoforms have distinct functions. In our research, we constructed a circANRIL overexpression plasmid, transfected it into HEK-293T cell line, and explored potential core genes and signaling pathways related to the important differential mechanisms between the circANRIL-overexpressing cell line and control cells through bioinformatics analysis. Methods Stable circANRIL-overexpressing (circANRIL-OE) HEK-293T cells and control cells were generated by infection with the circANRIL-OE lentiviral vector or a negative control vector, and successful transfection was confirmed by conventional flurescence microscopy and quantitative real-time PCR (qRT-PCR). Next, differentially expressed genes (DEGs) between circANRIL-OE cells and control cells were detected. Subsequently, Gene Ontology (GO) biological process (BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore the principal functions of the significant DEGs. A protein–protein interaction (PPI) network and competing endogenous RNA (ceRNA) network were constructed in Cytoscape to determine circularRNA (circRNA)- microRNA(miRNA)-messenger RNA (mRNA) interactions and hub genes, and qRT-PCR was used to verify changes in the expression of these identified target genes. Results The successful construction of circANRIL-OE cells was confirmed by plasmid sequencing, visualization with fluorescence microscopy and qRT-PCR. A total of 1745 DEGs between the circANRIL-OE group and control were identified, GO BP analysis showed that these genes were mostly related to RNA biosynthesis and processing, regulation of transcription and signal transduction. The KEGG pathway analysis showed that the up regulated DEGs were mainly enriched in the MAPK signaling pathway. Five associated target genes were identified in the ceRNA network and biological function analyses. The mRNA levels of these five genes and ANRIL were detected by qRT-PCR, but only COL5A2 and WDR3 showed significantly different expression in circANRIL-OE cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis for the identification of hub genes and signaling pathways related to circANRIL

Qin

Zheng

et al. 2022

PeerJ

View full text Add to dashboard Cite

show abstract

“…OSR1 is phosphorylated by WNK on residues Ser325 and Ser339 of the S-motif and Thr185 of the T-loop [28]. The phosphorylation of the S-motif of SPAK/OSR1 has recently been found to be important for their stability under osmotic stress [29]. However, the phosphorylation of the T-loop is required for their activation.…”

Section: Wnk-spak-ncc Kinase Pathwaymentioning

confidence: 99%

WNK-SPAK/OSR1-NCC kinase signaling pathway as a novel target for the treatment of salt-sensitive hypertension

Brown

Azlan

et al. 2020

Acta Pharmacol Sin

View full text Add to dashboard Cite

Hypertension is the most prevalent health condition worldwide, affecting ~1 billion people. Gordon's syndrome is a form of secondary hypertension that can arise due to a number of possible mutations in key genes that encode proteins in a pathway containing the With No Lysine [K] (WNK) and its downstream target kinases, SPS/Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress responsive kinase 1 (OSR1). This pathway regulates the activity of the thiazide-sensitive sodium chloride cotransporter (NCC), which is responsible for NaCl reabsorption in the distal nephron. Therefore, mutations in genes encoding proteins that regulate the NCC proteins disrupt ion homeostasis and cause hypertension by increasing NaCl reabsorption. Thiazide diuretics are currently the main treatment option for Gordon's syndrome. However, they have a number of side effects, and chronic usage can lead to compensatory adaptations in the nephron that counteract their action. Therefore, recent research has focused on developing novel inhibitory molecules that inhibit components of the WNK-SPAK/OSR1-NCC pathway, thereby reducing NaCl reabsorption and restoring normal blood pressure. In this review we provide an overview of the currently reported molecular inhibitors of the WNK-SPAK/OSR1-NCC pathway and discuss their potential as treatment options for Gordon's syndrome.

show abstract

“…The CRL4 complex is also regulated by phosphorylations and further posttranslational modifications ( 6 , 12 ). CRL4 was found to interact in a context-specific manner also with kinases, including oxidative stress-responsive kinase 1 (OSR1), cyclin-dependent kinase 1 (CDK1), inositol phosphate kinase (IP6 kinase), and ataxia telangiectasia and Rad3 related (ATR) ( 13 – 16 ), but their precise function for the regulation of CRL4 assembly and functions is still not clear.…”

Section: Introductionmentioning

confidence: 99%

MEKK1-Dependent Activation of the CRL4 Complex Is Important for DNA Damage-Induced Degradation of p21 and DDB2 and Cell Survival

Bacher

Stekman

Farah

et al. 2021

Molecular and Cellular Biology

View full text Add to dashboard Cite

Cullin-4 ubiquitin ligase (CRL4) complexes are differentially composed and highly dynamic protein assemblies that control many biological processes including the global genome nucleotide excision repair (GG-NER) pathway. Here we identified the kinase mitogen-activated protein kinase kinase kinase 1 (MEKK1) as a novel constitutive interactor of a cytosolic CRL4 complex that disassembles after DNA damage due to the Caspase-mediated cleavage of MEKK1. The kinase activity of MEKK1 was important to trigger auto-ubiquitination of the CRL4 complex by K48- and K63-linked ubiquitin chains. MEKK1 knockdown prohibited DNA damage-induced degradation of the CRL4 component DNA-damage binding protein 2 (DDB2) and the CRL4 substrate p21 and also cell recovery and survival. A ubiquitin replacement strategy revealed a contribution of K63-branched ubiquitin chains for DNA damage-induced DDB2/p21 decay, cell cycle regulation and cell survival. These data might have also implications for cancer, as frequently occurring mutations of MEKK1 might have an impact on genome stability and the therapeutic efficacy of CRL4-dependent immunomodulatory drugs such as thalidomide-derivatives.

show abstract

The Cul4‐DDB1‐WDR3/WDR6 Complex Binds SPAK and OSR1 Kinases in a Phosphorylation‐Dependent Manner

Cited by 13 publications

References 18 publications

Integrated bioinformatics analysis for the identification of hub genes and signaling pathways related to circANRIL

Integrated bioinformatics analysis for the identification of hub genes and signaling pathways related to circANRIL

WNK-SPAK/OSR1-NCC kinase signaling pathway as a novel target for the treatment of salt-sensitive hypertension

MEKK1-Dependent Activation of the CRL4 Complex Is Important for DNA Damage-Induced Degradation of p21 and DDB2 and Cell Survival

Contact Info

Product

Resources

About