Dataset Information

N-myristoylation by NMT1 is POTEE-dependent to stimulate liver tumorigenesis via differentially regulating ubiquitination of targets

ABSTRACT: Here, N-myristolyation, one kind post-translational modification, and its enzyme NMT1 but not NMT2, were found to be critical in liver cancer. Two categories of proteins, i.e. N-myristolyation down-regulated (NDP) and up-regulated protein (NUP) were revealed negatively and positively regulated by NMT1, respectively. Both NDP and NUP could be N-myristolyated by NMT1 indispensible of POTEE. However, N-myristolyation decreased and increased stability of NDP and NUP, respectively. NDP-specific binding protein RPL7A facilitated HISTIH4H, which has ubiquitin E3 ligase function, to ubiquitinate NDP. By contrast, NUP-specific binding protein HBB prevented NUP from ubiquitination by HISTIH4H. Notably, function of RPL7A and HBB were all NMT1-dependent. Moreover, NDP suppressed while NUP stimulated transformative phenotypes. Clinically, higher levels of NMT1 and NUP with lower levels of NDP had worse prognostic outcome. Collectively, N-myristolyation by NMT1 suppresses anti-tumorigenic NDP, whereas stimulates pro-tumorigenic NUP by interfering their ubiquitination to finally result in a pro-tumorigenic outcome in liver cancer.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Liver

SUBMITTER: Rachel Green

LAB HEAD: Jiayi Wang

PROVIDER: PXD011764 | Pride | 2021-09-08

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 12

Publications

N-Myristoylation by NMT1 Is POTEE-Dependent to Stimulate Liver Tumorigenesis <i>via</i> Differentially Regulating Ubiquitination of Targets.

Zhu Guoqing G Wang Feng F Li Haojie H Zhang Xiao X Wu Qi Q Liu Ya Y Qian Mingping M Guo Susu S Yang Yueyue Y Xue Xiangfei X Sun Fenyong F Qiao Yongxia Y Pan Qiuhui Q

Frontiers in oncology 20210531

<h4>Background</h4>A tremendous amount of studies have suggested that post-translational modifications (PTMs) play pivotal roles during tumorigenesis. Compared to other PTMs, lipid modification is less studied. Recently, N-myristoylation, one type of lipid modification, has been paid attention to the field of cancer. However, whether and how N-myristoylation exerts its roles in liver tumorigenesis still remains unclear.<h4>Methods</h4>Parallel reaction monitoring (PRM) was conducted to evaluate ...[more]

PMID: 34136404

Similar Datasets

Project description:Arachidonic acid (AA) is a polyunsaturated fatty acid present at high concentrations in the ovarian cancer (OC) microenvironment and is associated with poor clinical outcome. In the present study, we elucidate a potential link between AA and pro-tumorigenic macrophage polarization. Methods: AA-triggered signal transduction was studied in primary monocyte-derived macrophages (MDMs) by phosphoproteomics, transcriptional profiling, measurement of intracellular Ca2+ accumulation and reactive oxygen species production in conjunction with bioinformatic analyses. Functional effects were investigated by actin filament staining, quantification of macropinocytosis and analysis of extracellular vesicle release. Results: We identified the ASK1 - p38 (MAPK13/14) axis as a central constituent of signal transduction pathways triggered by non-metabolized AA. This pathway was induced by the Ca2+-triggered activation of calmodulin kinase II, and to a minor extent by ROS generation in a subset of donors. Activated p38 in turn was linked to a transcriptional stress response associated with a poor relapse-free survival. Consistent with the phosphorylation of the p38 substrate HSP27 and the (de)phosphorylation of multiple regulators of Rho family GTPases, AA impaired actin filament organization and inhibited actin-driven macropinocytosis. AA also affected the phosphorylation of proteins regulating vesicle biogenesis, and consistently, AA enhanced the release of tetraspanin-containing exosomes. Finally, we identified phospholipase A2 Group 2A (PLA2G2A) as the clinically most relevant enzyme producing extracellular AA, providing further potentially theranostic options. Conclusion: Our results suggest that AA contributes to an unfavorable clinical outcome of OC by promoting the pro-tumorigenic phenotype of tumor-associated macrophages. Besides critical AA-regulated signal transduction proteins identified in the present study, PLA2G2A might represent a potential prognostic tool and therapeutic target to interfere with OC progression.

Project description:To cause disease, Salmonella enterica serovar Typhimurium requires two type-III secretion systems, encoded on Salmonella Pathogenicity Islands 1 and 2 (SPI-1 and -2). These secretion systems serve to deliver virulence proteins, termed effectors, into the host cell cytosol. While the importance of these effector proteins to promote colonization and replication within the host has been established, the specific roles of individual secreted effectors in the disease process are not well understood. In this study, we used an in vivo gallbladder epithelial cell infection model to study the function of the SPI-2-encoded effector, SseL. Deletion of the sseL gene resulted in bacterial filamentation and elongation and unusual localization of Salmonella within infected epithelial cells. Infection with the ?sseL strain also caused dramatic changes in lipid metabolism and led to massive accumulation of lipid droplets in infected cells. Some of these changes were investigated through metabolomics of gallbladder tissue. This phenotype was directly attributed to the deubiquitinase activity of SseL, as a Salmonella strain carrying a single point mutation in the catalytic cysteine resulted in the same phenotype as the deletion mutant. Excessive buildup of lipids due to the absence of a functional sseL gene was also observed in S. Typhimurium-infected livers. These results demonstrate that SseL alters host lipid metabolism in infected epithelial cells by modifying ubiquitination patterns of cellular targets. Female C57BL/6 mice were infected with the indicated strain of Salmonella enterica serovar Typhimurium by oral gavage. Four gallbladders were collected and pooled per sample group and metabolites extracted using a mixture of methanol and chloroform. Extracts were infused into a 12-T Apex-Qe hybrid quadrupole-FT-ICR mass spectrometer equipped with an Apollo II electrospray ionization source, a quadrupole mass filter and a hexapole collision cell. Raw mass spectrometry data were processed as described elsewhere (Han et al. 2008. Metabolomics. 4:128-140). To identify differences in metabolite composition between different groups of samples, we filtered the list of masses for metabolites which were present on one set of samples but not the other. Additionally, we calculated the ratios between averaged intensities of metabolites from each group of mice. To assign possible metabolite identities, monoisotopic neutral masses of interest were queried against MassTrix (http://masstrix.org). Masses were searched against the Mus musculus database within a mass error of 3 ppm.

			Action	DRS
	S8014PRM_C1.raw	Raw
	S8014PRM_C2.raw	Raw
	S8014PRM_C3.raw	Raw
	S8014PRM_C4.raw	Raw
	S8014PRM_C5.raw	Raw