FBXO32 targets PHPT1 for ubiquitination to regulate the growth of EGFR mutant lung cancer

Zhang, Ning; Liao, Yifeng; Lv, Weize; Zhu, Shunda; Qiu, Yeqing; Chen, Nan; Xiao, Mei; Zhang, Hongyu

doi:10.1007/s13402-022-00669-6

Cited by 15 publications

(13 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The importance of pHis to higher eukaryotes is further illustrated by the growing number of histidine kinases, phosphotransferases [ 46 ] and phosphatases that have been characterised. This includes the NME family of likely histidine kinases [ 47 , 48 ], as well as the protein histidine phosphatase LHPP which has multifaceted activity as a tumour suppressor for a range of cancers [ 12 , 14 ], and the histidine phosphatase PHPT1, which is an oncogene involved in lung cancer [ 49 ]. To date there is good evidence for these proteins’ involvement in cancers, but little biochemical evidence that their function is due to histidine phosphorylation/dephosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Quantitation of phosphohistidine in proteins in a mammalian cell line by 31P NMR

et al. 2022

View full text Add to dashboard Cite

There is growing evidence to suggest that phosphohistidines are present at significant levels in mammalian cells and play a part in regulating cellular activity, in particular signaling pathways related to cancer. Because of the chemical instability of phosphohistidine at neutral or acid pH, it remains unclear how much phosphohistidine is present in cells. Here we describe a protocol for extracting proteins from mammalian cells in a way that avoids loss of covalent phosphates from proteins, and use it to measure phosphohistidine concentrations in human bronchial epithelial cell (16HBE14o-) lysate using 31P NMR spectroscopic analysis. Phosphohistidine is determined on average to be approximately one third as abundant as phosphoserine and phosphothreonine combined (and thus roughly 15 times more abundant than phosphotyrosine). The amount of phosphohistidine, and phosphoserine/phosphothreonine per gram of protein from a cell lysate was determined to be 23 μmol/g and 68 μmol/g respectively. The amount of phosphohistidine, and phosphoserine/phosphothreonine per cell was determined to be 1.8 fmol/cell, and 5.8 fmol/cell respectively. Phosphorylation is largely at the N3 (tele) position. Typical tryptic digest conditions result in loss of most of the phosphohistidine present, which may explain why the amounts reported here are greater than is generally seen using mass spectroscopy assays. The results further strengthen the case for a functional role of phosphohistidine in eukaryotic cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Quantitation of phosphohistidine in proteins in a mammalian cell line by 31P NMR

et al. 2022

View full text Add to dashboard Cite

show abstract

“…FBXO32 targets c-Myc for proteasomal degradation and inhibits c-Myc activity [ 39 ]. It acts as an E3 ubiquitin ligase and suppresses breast cancer and lung cancer tumorigenesis [ 40 , 41 ]. FBXO32 can be modulated by LINC00494 to facilitate ovarian cancer progression via binding with NF-κB [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Androgen-Responsive Oncogenic lncRNA RP11-1023L17.1 Enhances c-Myc Protein Stability in Prostate Cancer

Huang

Chen

et al. 2022

IJMS

View full text Add to dashboard Cite

Long noncoding RNAs (lncRNAs) have been found as novel participants in the pathophysiology of prostate cancer (PCa), which is predominantly regulated by androgen and its receptor. The biological function of androgen-responsive lncRNAs remains poorly understood. Here, we identified that lncRNA RP11-1023L17.1, which is highly expressed in PCa. RP11-1023L17.1 expression, can be directly repressed by the androgen receptor in PCa cells. RP11-1023L17.1 depletion inhibited the proliferation, migration, and cell cycle progression, and promoted the apoptosis of PCa cells, indicating that RP11-1023L17.1 acts as an oncogene in PCa cells. Microarray results revealed that RP11-1023L17.1 depletion downregulated the c-Myc transcription signature in PCa cells. RP11-1023L17.1 depletion-induced cellular phenotypes can be overcome by ectopically overexpressed c-Myc. Mechanistically, RP11-1023L17.1 represses FBXO32 mRNA expression, thereby enhancing c-Myc protein stability by blocking FBXO32-mediated c-Myc degradation. Our findings reveal the previously unrecognized roles of RP11-1023L17.1 in c-Myc-dependent PCa tumorigenesis.

show abstract

“…FBXO32 has been involved in carcinogenesis and tumor malignant behaviors. FBXO32 worked as an E3 ligase for PHPT1 ubiquitination, leading to reduction of PHPT1 accumulation, inactivation of the ERK/MAPK axis, which inhibited the proliferation of lung cancer cells ( 153 ). FBXO32 repressed tumorigenesis by targeting KLF4 for ubiquitination and proteasomal degradation in breast cancer ( 154 ).…”

Section: Lncrnas Regulate the Expression Of F-box Proteinsmentioning

confidence: 99%

The functions of long noncoding RNAs on regulation of F-box proteins in tumorigenesis and progression

et al. 2022

View full text Add to dashboard Cite

Accumulated evidence has revealed that F-box protein, a subunit of SCF E3 ubiquitin ligase complexes, participates in carcinogenesis and tumor progression via targeting its substrates for ubiquitination and degradation. F-box proteins could be regulated by cellular signaling pathways and noncoding RNAs in tumorigenesis. Long noncoding RNA (lncRNA), one type of noncoding RNAs, has been identified to modulate the expression of F-box proteins and contribute to oncogenesis. In this review, we summarize the role and mechanisms of multiple lncRNAs in regulating F-box proteins in tumorigenesis, including lncRNAs SLC7A11-AS1, MT1JP, TUG1, FER1L4, TTN-AS1, CASC2, MALAT1, TINCR, PCGEM1, linc01436, linc00494, GATA6-AS1, and ODIR1. Moreover, we discuss that targeting these lncRNAs could be helpful for treating cancer via modulating F-box protein expression. We hope our review can stimulate the research on exploration of molecular insight into how F-box proteins are governed in carcinogenesis. Therefore, modulation of lncRNAs is a potential therapeutic strategy for cancer therapy via regulation of F-box proteins.

show abstract

FBXO32 targets PHPT1 for ubiquitination to regulate the growth of EGFR mutant lung cancer

Cited by 15 publications

References 48 publications

Quantitation of phosphohistidine in proteins in a mammalian cell line by 31P NMR

Quantitation of phosphohistidine in proteins in a mammalian cell line by 31P NMR

Androgen-Responsive Oncogenic lncRNA RP11-1023L17.1 Enhances c-Myc Protein Stability in Prostate Cancer

The functions of long noncoding RNAs on regulation of F-box proteins in tumorigenesis and progression

Contact Info

Product

Resources

About