Transglutaminase-mediated cross-linking of WDR54 regulates EGF receptor-signaling

Maeda, Akane; Nishino, Tasuku; Matsunaga, Ryota; Yokoyama, Atsushi; Suga, Hiroshi; Yagi, Toshiki; Konishi, Hiroaki

doi:10.1016/j.bbamcr.2018.11.009

Cited by 8 publications

(9 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent study reported that WDR54 could activate the AKT, ERK, or β-catenin signaling pathways and promote cell proliferation in colorectal cancer and bladder cancer 25,26. Mechanistically, WDR54 was found to be cross-linked by the action of transgluaminase, resulting in the activation of the EGF receptor-mediated signaling pathway 27. In this study, we revealed that WDR54 was highly expressed in T-ALL cells and exhibited an oncogenic function in T-ALL.…”

mentioning

confidence: 66%

See 1 more Smart Citation

WDR54 exerts oncogenic roles in T‐cell acute lymphoblastic leukemia

Li,

Zhang,

et al. 2023

Cancer Science

View full text Add to dashboard Cite

WDR54 has been recently identified as a novel oncogene in colorectal and bladder cancers. However, the expression and function of WDR54 in T-cell acute lymphoblastic leukemia (T-ALL) were not reported. In this study, we investigated the expression of WDR54 in T-ALL, as well as its function in T-ALL pathogenesis using cell lines and T-ALL xenograft. Bioinformatics analysis indicated high mRNA expression of WDR54 in T-ALL. We further confirmed that the expression of WDR54 was significantly elevated in T-ALL. Depletion of WDR54 dramatically inhibited cell viability and induced apoptosis and cell cycle arrest at S phase in T-ALL cells in vitro. Moreover, knockdown of WDR54 impeded the process of leukemogenesis in a Jurkat xenograft model in vivo. Mechanistically, the expression of PDPK1, phospho-AKT (p-AKT), total AKT, phospho-ERK (p-ERK), Bcl-2 and Bcl-xL were downregulated, while cleaved caspase-3 and cleaved caspase-9 were upregulated in T-ALL cells with WDR54 knockdown.Additionally, RNA-seq analysis indicated that WDR54 might regulate the expression of some oncogenic genes involved in multiple signaling pathways. Taken together, these findings suggest that WDR54 may be involved in the pathogenesis of T-ALL and serve as a potential therapeutic target for the treatment of T-ALL.

show abstract

mentioning

confidence: 66%

“…WDR54 could promote cell proliferation by activating AKT, ERK, and β‐catenin signaling in cancers 25,26 . Mechanistically, the cross‐linking and ubiquitination of WDR54 were found to regulate ERK activity in response to EGF stimulation 27 . These studies suggest that WDR54 may be involved in the proliferation of tumors.…”

Section: Introductionmentioning

confidence: 88%

WDR54 exerts oncogenic roles in T‐cell acute lymphoblastic leukemia

Li,

Zhang,

et al. 2023

Cancer Science

View full text Add to dashboard Cite

show abstract

“…Another group of proteins whose expression was modified is associated with the organization and functions of extra-cellular matrix (ECM) and structural proteins ( Table S6 , Figure 8D ), which were found to be significantly reduced (3–17-fold), while others increased 2–6 fold. The downregulated proteins included tensin-4 (TNS4), which is involved in cell migration and links the signal transduction pathways to the cytoskeleton; and protein-glutamine gamma-glutamyltransferase 2 (TGM2), catalyzing the cross-linking of proteins between Gln and Lys residues ( 40 ). Several cell adhesion proteins such as G-protein coupled receptor G1 (ADGRG1), plakophilin-2 (PKP2), and claudin-2 (CLDN2) were also significantly reduced.…”

Section: Resultsmentioning

confidence: 99%

Non-apoptotic activity of the mitochondrial protein SMAC/Diablo in lung cancer: Novel target to disrupt survival, inflammation, and immunosuppression

et al. 2022

View full text Add to dashboard Cite

Mitochondrial SMAC/Diablo induces apoptosis by binding the inhibitor of apoptosis proteins (IAPs), thereby activating caspases and, subsequently, apoptosis. Previously, we found that despite its pro-apoptotic activity, SMAC/Diablo is overexpressed in cancer, and demonstrated that in cancer it possesses new essential and non-apoptotic functions that are associated with regulating phospholipid synthesis including modulating mitochondrial phosphatidylserine decarboxylase activity. Here, we demonstrate additional functions for SMAC/Diablo associated with inflammation and immunity. CRISPR/Cas9 SMAC/Diablo-depleted A549 lung cancer cells displayed inhibited cell proliferation and migration. Proteomics analysis of these cells revealed altered expression of proteins associated with lipids synthesis and signaling, vesicular transport and trafficking, metabolism, epigenetics, the extracellular matrix, cell signaling, and neutrophil-mediated immunity. SMAC-KO A549 cell-showed inhibited tumor growth and proliferation and activated apoptosis. The small SMAC-depleted “tumor” showed a morphology of alveoli-like structures, reversed epithelial-mesenchymal transition, and altered tumor microenvironment. The SMAC-lacking tumor showed reduced expression of inflammation-related proteins such as NF-kB and TNF-α, and of the PD-L1, associated with immune system suppression. These results suggest that SMAC is involved in multiple processes that are essential for tumor growth and progression. Thus, targeting SMAC’s non-canonical function is a potential strategy to treat cancer.

show abstract

“…The consistency of TGM2 down‐regulated in EAT and plasma level indicate that TGM2 as a potential molecule plays an important role in HFrEF/HFmrEF patients. TGM2 is a calcium‐dependent acyltransferase which catalyses the formation of covalent bonds between peptide‐bound glutamine and various other amines, such as gamma‐amino group of peptide‐bound lysine, or mono‐and polyamines, thereby implicating the cross‐linking of proteins such as ACO2, HSPB6, FN1, HMGB1, RAP1GDS1, SPP1 24,25 and the conjugation of polyamines to proteins 26,27 . It involves in many biological processes, such as chromatin modification and apoptosis, cellular differentiation, angiogenesis, bone development and wound healing 28 .…”

Section: Discussionmentioning

confidence: 99%

Proteomic profiling of epicardial fat in heart failure with preserved versus reduced and mildly reduced ejection fraction

Gao

Peng

et al. 2023

J Cellular Molecular Medi

View full text Add to dashboard Cite

In order to explore the proteomic signatures of epicardial adipose tissue (EAT) related to the mechanism of heart failure with reduced and mildly reduced ejection fraction (HFrEF/HFmrEF) and heart failure (HF) with preserved ejection fraction (HFpEF), a comprehensive proteomic analysis of EAT was made in HFrEF/HFmrEF (n = 5) and HFpEF (n = 5) patients with liquid chromatography–tandem mass spectrometry experiments. The selected differential proteins were verified between HFrEF/HFmrEF (n = 20) and HFpEF (n = 40) by ELISA (enzyme‐linked immunosorbent assay). A total of 599 EAT proteins were significantly different in expression between HFrEF/HFmrEF and HFpEF. Among the 599 proteins, 58 proteins increased in HFrEF/HFmrEF compared to HFpEF, whereas 541 proteins decreased in HFrEF/HFmrEF. Of these proteins, TGM2 in EAT was down‐regulated in HFrEF/HFmrEF patients and was confirmed to decrease in circulating plasma of the HFrEF/HFmrEF group (p = 0.019). Multivariate logistic regression analysis confirmed plasma TGM2 could be an independent predictor of HFrEF/HFmrEF (p = 0.033). Receiver operating curve analysis indicated that the combination of TGM2 and Gensini score improved the diagnostic value of HFrEF/HFmrEF (p = 0.002). In summary, for the first time, we described the proteome in EAT in both HFpEF and HFrEF/HFmrEF and identified a comprehensive dimension of potential targets for the mechanism behind the EF spectrum. Exploring the role of EAT may offer potential targets for preventive intervention of HF.

show abstract

Transglutaminase-mediated cross-linking of WDR54 regulates EGF receptor-signaling

Cited by 8 publications

References 37 publications

WDR54 exerts oncogenic roles in T‐cell acute lymphoblastic leukemia

WDR54 exerts oncogenic roles in T‐cell acute lymphoblastic leukemia

Non-apoptotic activity of the mitochondrial protein SMAC/Diablo in lung cancer: Novel target to disrupt survival, inflammation, and immunosuppression

Proteomic profiling of epicardial fat in heart failure with preserved versus reduced and mildly reduced ejection fraction

Contact Info

Product

Resources

About