Critical role of protein L-isoaspartyl methyltransferase in basic fibroblast growth factor-mediated neuronal cell differentiation

Dung, To Thi Mai; Yi, Young-Su; Heo, Jieun; Yang, Woo Seok; Kim, Ji Hye; Kim, Han Gyung; Park, Jae Gwang; Yoo, Byong Chul; Cho, Jae Youl; Hong, Sungyoul

doi:10.5483/bmbrep.2016.49.8.020

Cited by 8 publications

(4 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…VEGF silencing suppresses the proliferation of human SaOS-2 cells and reduces angiogenesis by inactivating the VEGF/PI3K/AKT pathway. Additionally, VEGF expression is regarded to be repressed by HDACs, especially HDAC4 ( 33 ). Moreover, an mTOR inhibitor attenuates osteoblast differentiation of human periodontal ligament cells and osteoblasts ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

HDAC inhibitor LMK‑235 promotes the odontoblast differentiation of dental pulp cells

et al. 2017

View full text Add to dashboard Cite

The role of dental pulp cells (DPCs) in hard dental tissue regeneration had received increasing attention because DPCs can differentiate into odontoblasts and other tissue-specific cells. In recent years, epigenetic modifications had been identified to serve an important role in cell differentiation, and histone deacetylase (HDAC) inhibitors have been widely studied by many researchers. However, the effects of HDAC4 and HDAC5 on the differentiation of DPCs and the precise molecular mechanisms remain unclear. The present study demonstrated that LMK-235, a specific human HDAC4 and HDAC5 inhibitor, increased the expression of specific odontoblastic gene expression levels detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in dental pulp cells, and did not reduce cell proliferation tested by MTT assay after 3 days in culture at a low concentration. In addition, the mRNA and protein expression levels of dentin sialophosphoprotein, runt-related transcription factor 2, alkaline phosphatase (ALP) and osteocalcin were evaluated by RT-qPCR and western blotting, respectively. The increased gene and protein expression of specific markers demonstrated, indicating that LMK-235 promoted the odontoblast induction of DPCs. ALP activity and mineralised nodule formation were also enhanced due to the effect of LMK-235, detected by an ALP activity test and Alizarin Red S staining, respectively. Additionally, the vascular endothelial growth factor (VEGF)/RAC-gamma serine/threonine-protein kinase (AKT)/mechanistic target of rapamycin (mTOR) signalling pathway was tested to see if it takes part in the differentiation of DPCs treated with LMK-235, and it was demonstrated that the mRNA expression levels of VEGF, AKT and mTOR were upregulated. These findings indicated that LMK-235 may serve a key role in the proliferation and odontoblast differentiation of DPCs, and could be used to accelerate dental tissue regeneration.

show abstract

Section: Discussionmentioning

confidence: 99%

HDAC inhibitor LMK‑235 promotes the odontoblast differentiation of dental pulp cells

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In humans, single nucleotide polymorphisms in gene encoding PIMT ( Pcmt1 ) have been associated with a risk of spina bifida and premature ovarian failure [ 37 ]. Because of the relevance of PIMT, most studies have investigated its physiological functions linked to aged protein repair or its role in the pathogenesis of Alzheimer’s disease [ 38 ].…”

Section: Resultsmentioning

confidence: 99%

PIMT Binding to C-Terminal Ala459 of CAIX Is Involved in Inside-Out Signaling Necessary for Its Catalytic Activity

Simko

Belvončíková

Csáderová

et al. 2020

IJMS

View full text Add to dashboard Cite

Human carbonic anhydrase IX (CAIX), a unique member of the α carbonic anhydrase family, is a transmembrane glycoprotein with high enzymatic activity by which CAIX contributes to tumorigenesis through pH regulation. Due to its aberrant expression, CAIX is considered to be a marker of tumor hypoxia and a poor prognostic factor of several human cancers. Hypoxia-activated catalytic function of CAIX is dependent on posttranslational modification of its short intracellular domain. In this work, we have identified that C-terminal Ala459 residue, which is common across CAIX of various species as well as additional transmembrane isoforms, plays an important role in CAIX activation and in pH regulation. Moreover, structure prediction I-TASSER analysis revealed involvement of Ala459 in potential ligand binding. Using tandem mass spectrometry, Protein-L-isoaspartyl methyltransferase (PIMT) was identified as a novel interacting partner, further confirmed by an in vitro pulldown assay and an in situ proximity ligation assay. Indeed, suppression of PIMT led to increased alkalinization of culture media of C33a cells constitutively expressing CAIX in hypoxia. We suggest that binding of PIMT represents a novel intracellular signal required for enzymatic activity of CAIX with a potential unidentified downstream function.

show abstract

“…In the brain, PCMT1 reportedly regulates the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway, as increased AKT/GSK3b signaling is seen in the hippocampus of Pcmt1 knockout mice. 74,75 Additionally, GSK3b phosphorylation at serine 9, which inhibits GSK3b function, was low in Pcmt1 +/+ mice, indicating an abundance of activated GSK3b, and this suggests that Pcmt1 and GSK3b may function in a positive feedback loop. 76 Considering that PKCq and GSK3b work in opposition, it is interesting to speculate that GSK3b may phosphorylate PCMT1 to regulate its function when PKCq activity is inhibited in iTregs.…”

Section: Discussionmentioning

confidence: 98%

Protein Kinase C Theta Modulates PCMT1 through hnRNPL to Regulate FOXP3 Stability in Regulatory T Cells

et al. 2020

View full text Add to dashboard Cite

T cell receptor signaling, together with cytokine-induced signals, can differentially regulate RNA processing to influence T helper versus regulatory T cell fate. Protein kinase C family members have been shown to function in alternative splicing and RNA processing in various cell types. T cell-specific protein kinase C theta, a molecular regulator of T cell receptor downstream signaling, has been shown to phosphorylate splicing factors and affect post-transcriptional control of T cell gene expression. In this study, we explored how using a synthetic cell-penetrating peptide mimic for intracellular anti-protein kinase C theta delivery fine-tunes differentiation of induced regulatory T cells through its differential effects on RNA processing. We identified protein kinase C theta signaling as a critical modulator of two key RNA regulatory factors, heterogeneous nuclear ribonucleoprotein L (hnRNPL) and protein-Lisoaspartate O-methyltransferase-1 (PCMT1), and loss of protein kinase C theta function initiated a "switch" in post-transcriptional organization in induced regulatory T cells. More interestingly, we discovered that protein-L-isoaspartate Omethyltransferase-1 acts as an instability factor in induced regulatory T cells, by methylating the forkhead box P3 (FOXP3) promoter. Targeting protein-L-isoaspartate O-methyltransferase-1 using a cell-penetrating antibody revealed an efficient means of modulating RNA processing to confer a stable regulatory T cell phenotype.

show abstract

Critical role of protein L-isoaspartyl methyltransferase in basic fibroblast growth factor-mediated neuronal cell differentiation

Cited by 8 publications

References 43 publications

HDAC inhibitor LMK‑235 promotes the odontoblast differentiation of dental pulp cells

HDAC inhibitor LMK‑235 promotes the odontoblast differentiation of dental pulp cells

PIMT Binding to C-Terminal Ala459 of CAIX Is Involved in Inside-Out Signaling Necessary for Its Catalytic Activity

Protein Kinase C Theta Modulates PCMT1 through hnRNPL to Regulate FOXP3 Stability in Regulatory T Cells

Contact Info

Product

Resources

About