Proteomics

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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

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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]

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