PHD3 inhibits cell proliferation through hydroxylation of PAX2 at proline 9

Lun, Jie; Wang, Yuxin; Gao, Qiang; Wang, Yu; Zhang, Hongwei; Fang, Jing

doi:10.3724/abbs.2022043

Cited by 3 publications

(2 citation statements)

References 37 publications

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“…Previous studies have shown that downregulation of PAX gene expression in cancer cells leads to reduced cell proliferation and induction of apoptosis [21][22][23]. In our earlier investigations [20], we provided evidence indicating that depletion of PAX8 in RCC cell lines led to growth inhibition and initiation of senescence.…”

Section: Effects Of Pax2 or Pax8 Knockdown On A498 Cell Proliferationmentioning

confidence: 52%

Co-Expression of Multiple PAX Genes in Renal Cell Carcinoma (RCC) and Correlation of High PAX Expression with Favorable Clinical Outcome in RCC Patients

Li,

Almomani

et al. 2023

IJMS

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Renal cell carcinoma (RCC) is the most common form of kidney cancer, consisting of multiple distinct subtypes. RCC has the highest mortality rate amongst the urogenital cancers, with kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and kidney chromophobe carcinoma (KICH) being the most common subtypes. The Paired-box (PAX) gene family encodes transcription factors, which orchestrate multiple processes in cell lineage determination during embryonic development and organogenesis. Several PAX genes have been shown to be expressed in RCC following its onset and progression. Here, we performed real-time quantitative polymerase chain reaction (RT-qPCR) analysis on a series of human RCC cell lines, revealing significant co-expression of PAX2, PAX6, and PAX8. Knockdown of PAX2 or PAX8 mRNA expression using RNA interference (RNAi) in the A498 RCC cell line resulted in inhibition of cell proliferation, which aligns with our previous research, although no reduction in cell proliferation was observed using a PAX2 small interfering RNA (siRNA). We downloaded publicly available RNA-sequencing data and clinical histories of RCC patients from The Cancer Genome Atlas (TCGA) database. Based on the expression levels of PAX2, PAX6, and PAX8, RCC patients were categorized into two PAX expression subtypes, PAXClusterA and PAXClusterB, exhibiting significant differences in clinical characteristics. We found that the PAXClusterA expression subgroup was associated with favorable clinical outcomes and better overall survival. These findings provide novel insights into the association between PAX gene expression levels and clinical outcomes in RCC patients, potentially contributing to improved treatment strategies for RCC.

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Section: Effects Of Pax2 or Pax8 Knockdown On A498 Cell Proliferationmentioning

confidence: 52%

Co-Expression of Multiple PAX Genes in Renal Cell Carcinoma (RCC) and Correlation of High PAX Expression with Favorable Clinical Outcome in RCC Patients

Li,

Almomani

et al. 2023

IJMS

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“…Modifications of proteins, such as glycosylation, phosphorylation, or sumoylation, can result in altered migration on SDS-PAGE. Prolyl residues of proteins can be hydroxylated, and this modification may be involved in many important cellular processes, including oxygen sensing [10] , epigenetic regulation [11] , cell proliferation [12] , and viral biogenesis [13] . To investigate whether the altered migration is due to point mutations in different cell types, we introduced both SRP14 WT and SRP14 P124A into various cell lines.…”

Section: Resultsmentioning

confidence: 99%

The P124A mutation of SRP14 alters its migration on SDS-PAGE without impacting its function

Liu,

Zhou

2024

ABBS

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SRP14 is a crucial protein subunit of the signal recognition particle (SRP), a ribonucleoprotein complex essential for co-translational translocation to the endoplasmic reticulum. During our investigation of SRP14 expression across diverse cell lines, we observe variations in its migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), with some cells exhibiting slower migration and others migrating faster. However, the cause of this phenomenon remains elusive. Our research rules out alternative splicing as the cause and, instead, identifies the presence of a P124A mutation in SRP14 (SRP14 P124A ) among the faster-migrating variants, while the slower-migrating variants lack this mutation. Subsequent ectopic expression of wild-type SRP14 P124 or SRP14 WT and SRP14 P124A in various cell lines confirms that the P124A mutation indeed leads to faster migration of SRP14. Further mutagenesis analysis shows that the P117A and A121P mutations within the alanine-rich domain at the C-terminus of SRP14 are responsible for migration alterations on SDS-PAGE, whereas mutations outside this domain, such as P39A, Y27F, and T45A, have no such effect. Furthermore, the ectopic expression of SRP14 WT and SRP14 P124A yields similar outcomes in terms of SRP RNA stability, cell morphology, and cell growth, indicating that SRP14 P124A represents a natural variant of SRP14 and retains comparable functionality. In conclusion, the substitution of proline for alanine in the alanine-rich tail of SRP14 results in faster migration on SDS-PAGE, but has little effect on its function.

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