ZDHHC16 modulates FGF/ERK dependent proliferation of neural stem/progenitor cells in the zebrafish telencephalon

Shi, Wei; Chen, Xueran; Wang, Fen; Gao, Ming; Yang, Yang; Du, Zhaoxia; Wang, Chen; Yao, Yao; He, Kun; Hao, Aijun

doi:10.1002/dneu.22372

Cited by 16 publications

(14 citation statements)

References 44 publications

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“…Its name Ablphilin stems from its ability to interact with the non-receptor tyrosine kinase c-Abl at the ER surface ( Li et al, 2002 ). ZDHHC16/Aph2 is essential for embryonic and postnatal survival, eye and heart development in mice ( Zhou et al, 2015 ), for the proliferation of neural stem cells, where it is involved in the activation of the FGF/erk pathways ( Shi et al, 2016 ) and was reported to play a role in DNA damage response ( Cao et al, 2016 ). Our findings raise the possibility that some of these effects may involve ZDHHC6.…”

Section: Discussionmentioning

confidence: 99%

Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade

Abrami

Dallavilla

Sandoz

et al. 2017

eLife

102

128

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S-Palmitoylation is the only reversible post-translational lipid modification. Knowledge about the DHHC palmitoyltransferase family is still limited. Here we show that human ZDHHC6, which modifies key proteins of the endoplasmic reticulum, is controlled by an upstream palmitoyltransferase, ZDHHC16, revealing the first palmitoylation cascade. The combination of site specific mutagenesis of the three ZDHHC6 palmitoylation sites, experimental determination of kinetic parameters and data-driven mathematical modelling allowed us to obtain detailed information on the eight differentially palmitoylated ZDHHC6 species. We found that species rapidly interconvert through the action of ZDHHC16 and the Acyl Protein Thioesterase APT2, that each species varies in terms of turnover rate and activity, altogether allowing the cell to robustly tune its ZDHHC6 activity.

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Section: Discussionmentioning

confidence: 99%

Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade

Abrami

Dallavilla

Sandoz

et al. 2017

eLife

102

128

View full text Add to dashboard Cite

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“…ZDHHC16 was a DHHC encoding protein, which was tightly correlated with protein palmitoylation in previous researches [39]. Wei Shi et al reported that ZDHHC16 acted as a vital regulator in the process of NSPCs proliferation [40]. Li Jian et al uncovered pivotal players for ZDHHC16 in the regulation of DNA damage responses and Atm activation [41].…”

Section: Discussionmentioning

confidence: 96%

Clinical Significance of Prognostic Alternative Splicing Signature in Tumor Immune Environment and Immune Therapy of Hepatocellular Carcinoma

Deng

et al. 2021

Preprint

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Background: Hepatocellular carcinoma (HCC) ranks the sixth prevalent tumors with high mortality globally. Alternative splicing (AS) drives protein diversity, the imbalance of which might act an important factor in tumorigenesis. We aimed to construct of AS-based prognostic signature and elucidate the role in tumor immune microenvironment (TIME) and immunotherapy in HCC.Methods: To determine the prognosis-related AS events, univariate Cox regression analysis was performed, followed by the development of prognostic signatures. The prognosis predictive ability of risk signature was validated and a predictive nomogram was constructed. To uncover the context of TIME in HCC, ESTIMATE R package, ssGSEA algorithm and CIBERSORT method and TIMER database exploration were performed. And the correlation of AS events with immune checkpoint blockade (ICB)-related genes was analyzed.Results: A total of 3294 AS events associated with survival of HCC patients were screened. Based on splicing subtypes, we then constructed eight AS prognostic signature with robust prognostic predictive accuracy. Furthermore, a quantitative nomogram exhibited robust validity in prognostic prediction of HCC. Besides, the consolidated signature was significantly correlated with TIME diversity and ICB-related genes. Finally, the splicing regulatory network uncovered the potential functions of splicing factors (SFs) in HCC.Conclusion: Herein, the AS events may contribute novel and robust indicators for the prognostic prediction of HCC. The AS-SF networks could open up new approach for investigation of potential regulatory mechanisms. And we revealed the pivotal player of AS events in context of TIME and immunotherapy, contributing to clinical decision-making and personalized prognosis monitoring of HCC.

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“…Embryos were immersed in 10 mM BrdU solution at 28.5 • C for 4 h after peeled off the chorion manually with #5 watchmaker's forceps, and then embryos were fixed with 4% paraformaldehyde overnight at 4 • C. The next day, embryos were incubated with anti-BrdU antibody overnight and washed with PBST. After incubation with HRP secondary antibody for 1 h, DAB staining was performed to observe BrdU-positive cells (Shi et al, 2016).…”

Section: Bromodeoxyuridine Assaymentioning

confidence: 99%

“…Embryos were incubated in 2 µg/ml acridine orange solution at 28.5 • C for 30 min in the dark after peeled off the chorion. The embryos were analyzed by fluorescence microscope after washing the embryos with PBS (Shi et al, 2016).…”

Section: Acridine Orange Stainingmentioning

confidence: 99%

Pcgf1 Regulates Early Neural Tube Development Through Histone Methylation in Zebrafish

Zhou

et al. 2021

Front. Cell Dev. Biol.

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The neural induction constitutes the initial step in the generation of the neural tube. Pcgf1, as one of six Pcgf paralogs, is a maternally expressed gene, but its role and mechanism in early neural induction during neural tube development have not yet been explored. In this study, we found that zebrafish embryos exhibited a small head and reduced or even absence of telencephalon after inhibiting the expression of Pcgf1. Moreover, the neural induction process of zebrafish embryos was abnormally activated, and the subsequent NSC self-renewal was inhibited after injecting the Pcgf1 MO. The results of in vitro also showed that knockdown of Pcgf1 increased the expression levels of the neural markers Pax6, Pou3f1, and Zfp521, but decreased the expression levels of the pluripotent markers Oct4, Hes1, and Nanog, which further confirmed that Pcgf1 was indispensable for maintaining the pluripotency of P19 cells. To gain a better understanding of the role of Pcgf1 in early development, we analyzed mRNA profiles from Pcgf1-deficient P19 cells using RNA-seq. We found that the differentially expressed genes were enriched in many functional categories, which related to the development phenotype, and knockdown of Pcgf1 increased the expression of histone demethylases. Finally, our results showed that Pcgf1 loss-of-function decreased the levels of transcriptional repression mark H3K27me3 at the promoters of Ngn1 and Otx2, and the levels of transcriptional activation mark H3K4me3 at the promoters of Pou5f3 and Nanog. Together, our findings reveal that Pcgf1 might function as both a facilitator for pluripotent maintenance and a repressor for neural induction.

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ZDHHC16 modulates FGF/ERK dependent proliferation of neural stem/progenitor cells in the zebrafish telencephalon

Cited by 16 publications

References 44 publications

Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade

Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade

Clinical Significance of Prognostic Alternative Splicing Signature in Tumor Immune Environment and Immune Therapy of Hepatocellular Carcinoma

Pcgf1 Regulates Early Neural Tube Development Through Histone Methylation in Zebrafish

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