Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth

Wang, Zheng; Li, Min; Jiang, Hongfei; Luo, Shudi; Shao, Fei; Xia, Yan; Yang, Mengke; Ren, Xiangle; Liu, Tong; Yan, Meisi; Qian, Xu; He, Haiyan; Guo, Dong; Duan, Yuran; Wu, Ke; Wang, Lei; Ji, Guimei; Yu-li, Shen; Li, Lin; Zheng, Peixiang; Dong, Bofei; Fang, Jing; Zheng, Min; Liang, Tingbo; Li, Haitao; Yu, Rilei; Xu, Daqian; Lu, Zhimin

doi:10.1038/s41556-022-01009-4

Cited by 27 publications

(27 citation statements)

References 48 publications

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“…Tumor formation and phenotype were determined by bioluminescence imaging and histological analysis of hematoxylin and eosin-stained sections. [28] The other subgroups, which consisted of nine mice, were monitored for survival. The results were analyzed using STATISTICA software and represented by Kaplan-Meier plots.…”

Section: Methodsmentioning

confidence: 99%

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EGFR‐Induced and c‐Src‐Mediated CD47 Phosphorylation Inhibits TRIM21‐Dependent Polyubiquitylation and Degradation of CD47 to Promote Tumor Immune Evasion

Wang

et al. 2023

Advanced Science

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Tumor cells often overexpress immune checkpoint proteins, including CD47, for immune evasion. However, whether or how oncogenic activation of receptor tyrosine kinases, which are crucial drivers in tumor development, regulates CD47 expression is unknown. Here, it is demonstrated that epidermal growth factor receptor (EGFR) activation induces CD47 expression by increasing the binding of c‐Src to CD47, leading to c‐Src‐mediated CD47 Y288 phosphorylation. This phosphorylation inhibits the interaction between the ubiquitin E3 ligase TRIM21 and CD47, thereby abrogating TRIM21‐mediated CD47 K99/102 polyubiquitylation and CD47 degradation. Knock‐in expression of CD47 Y288F reduces CD47 expression, increases macrophage phagocytosis of tumor cells, and inhibits brain tumor growth in mice. In contrast, knock‐in expression of CD47 K99/102R elicits the opposite effects compared to CD47 Y288F expression. Importantly, CD47‐SIRPα blockade with an anti‐CD47 antibody treatment significantly enhances EGFR‐targeted cancer therapy. In addition, CD47 expression levels in human glioblastoma (GBM) specimens correlate with EGFR and c‐Src activation and aggravation of human GBM. These findings elucidate a novel mechanism underlying CD47 upregulation in EGFR‐activated tumor cells and underscore the role of the EGFR‐c‐Src‐TRIM21‐CD47 signaling axis in tumor evasion and the potential to improve the current cancer therapy with a combination of CD47 blockade with EGFR‐targeted remedy.

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Section: Methodsmentioning

confidence: 99%

“…Tumor formation and phenotype were determined by bioluminescence imaging and histological analysis of hematoxylin and eosin‐stained sections. [ 28 ]…”

Section: Methodsmentioning

confidence: 99%

EGFR‐Induced and c‐Src‐Mediated CD47 Phosphorylation Inhibits TRIM21‐Dependent Polyubiquitylation and Degradation of CD47 to Promote Tumor Immune Evasion

Wang

et al. 2023

Advanced Science

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“…The method of fluorescence intensity quantification was described previously with some modifications [49][50][51]. Image J software was used to perform immunofluorescence quantification as followed: use the lasso tool to draw the nucleus area where the fluorescence intensity is to be measured, and measure its total fluorescence intensity and area.…”

Section: Immunofluorescence Stainingmentioning

confidence: 99%

The regulation loop of MARVELD1 interacting with PARP1 in DNA damage response maintains genome stability and promotes therapy resistance of cancer cells

et al. 2023

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The DNA damage response (DDR) plays crucial roles in cancer prevention and therapy. Poly(ADP-ribose) polymerase 1 (PARP1) mediates multiple signal transduction in the DDR as a master regulator. Uncovering the regulatory factors of PARP1 contributes to a more comprehensive view of tumorigenesis and treatment strategies. Here, we reveal that MARVELD1 acts as a mediator of DDR to perform early events and maintain genome stability. Mechanistically, PARP1 PARylates MARVELD1 at D102, D118 and D130, and in turn, MARVELD1 stabilizes PARP1 by enhancing NAA50-mediated acetylation, thus forming a positive feedback loop. MARVELD1 knockout mice and their embryo fibroblasts exhibit genomic instability and shorter half-life of PARP1. Moreover, MARVELD1 partnering with PARP1 facilitates resistance to genotoxic drugs and disrupts PARP inhibitor (PARPi) effect in PDX model of colorectal cancer (CRC). Overall, our results underline the link between MARVELD1 and PARP1 in therapeutic resistance based on DDR and provide new insights for clinical tumor therapy of PARPi.

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“…[4][5][6] As the rate-limiting gluconeogenic enzyme that catalyzes the hydrolysis of fructose 1,6-bisphosphate (F-1,6-BP) to fructose 6-phosphate (F-6-P), fructose 1,6-biphosphatase 1 (FBP1) has been reported as a protein phosphatase that dephosphorylates histone H3 at T11 and suppresses peroxisome proliferator-activated receptor α (PPARα)-mediated β-oxidation and subsequent fatty acid oxidation in mitochondria. 7 Given that protein phosphatases dephosphorylate different substrates in a cell signaling context-dependent manner, whether FBP1 can dephosphorylate a nonhistone protein remains unclear.…”

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confidence: 99%

“…9 Under energy stress, FBP1 was previously shown to translocate into the nucleus with the conversion from a tetramer to monomers and act as a protein phosphatase to dephosphorylate histone H3, in which C129 in a reduced state in the catalytic domain forms a covalent phospho-C129 intermediate. 7 Under cytokine stimulation or oxidative stress, FBP1 binds and dephosphorylates IκBα pS32/36 to suppress NFκB activation. 8 Consequently, deficiency or low expression of FBP1, which frequently occurs in many types of cancer, including clear cell renal cell carcinoma and hepatocellular carcinoma, leads to tumor cell advantages in growth, counteraction to metabolic stresses, and genotoxic stress, and immune evasion.…”

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confidence: 99%

Repurposing FBP1: dephosphorylating IκBα to suppress NFκB

et al. 2023

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Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth

Cited by 27 publications

References 48 publications

EGFR‐Induced and c‐Src‐Mediated CD47 Phosphorylation Inhibits TRIM21‐Dependent Polyubiquitylation and Degradation of CD47 to Promote Tumor Immune Evasion

EGFR‐Induced and c‐Src‐Mediated CD47 Phosphorylation Inhibits TRIM21‐Dependent Polyubiquitylation and Degradation of CD47 to Promote Tumor Immune Evasion

The regulation loop of MARVELD1 interacting with PARP1 in DNA damage response maintains genome stability and promotes therapy resistance of cancer cells

Repurposing FBP1: dephosphorylating IκBα to suppress NFκB

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