• BMB Reports
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• 제54권2호
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• pp.89-97
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• 2021

Post-transcriptional regulation is an indispensable cellular mechanism of gene expression control that dictates various cellular functions and cell fate decisions. Recently, various chemical RNA modifications, termed the "epitranscriptome," have been proposed to play crucial roles in the regulation of post-transcriptional gene expression. To date, more than 170 RNA modifications have been identified in almost all types of RNA. As with DNA modification-mediated control of gene expression, regulation of gene expression via RNA modification is also accomplished by three groups of proteins: writers, readers, and erasers. Several emerging studies have revealed that dysregulation in RNA modification is closely associated with tumorigenesis. Notably, the molecular outcomes of specific RNA modifications often have opposite cellular consequences. In this review, we highlight the current progress in the elucidation of the mechanisms of cancer development due to chemical modifications of various RNA species.

• Molecules and Cells
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• 제43권2호
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• pp.160-167
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• 2020

Runt-related transcription factor 2 (RUNX2) is a key transcription factor for bone formation and osteoblast differentiation. Various signaling pathways and mechanisms that regulate the expression and transcriptional activity of RUNX2 have been thoroughly investigated since the involvement of RUNX2 was first reported in bone formation. As the regulation of Runx2 expression by extracellular signals has recently been reviewed, this review focuses on the regulation of post-translational RUNX2 activity. Transcriptional activity of RUNX2 is regulated at the post-translational level by various enzymes including kinases, acetyl transferases, deacetylases, ubiquitin E3 ligases, and prolyl isomerases. We describe a sequential and linear causality between post-translational modifications of RUNX2 by these enzymes. RUNX2 is one of the most important osteogenic transcription factors; however, it is not a suitable drug target. Here, we suggest enzymes that directly regulate the stability and/or transcriptional activity of RUNX2 at a post-translational level as effective drug targets for treating bone diseases.

• BMB Reports
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• 제44권3호
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• pp.147-157
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• 2011

The meiotic process from the primordial stage to zygote in female germ cells is mainly adjusted by post-transcriptional regulation of pre-existing maternal mRNA and post-translational modification of proteins. Several key proteins such as the cell cycle regulator, Cdk1/cyclin B, are post-translationally modified for precise control of meiotic progression. The second messenger (cAMP), kinases (PKA, Akt, MAPK, Aurora A, CaMK II, etc), phosphatases (Cdc25, Cdc14), and other proteins (G-protein coupled receptor, phosphodiesterase) are directly or indirectly involved in this process. Many proteins, such as CPEB, maskin, eIF4E, eIF4G, 4E-BP, and 4E-T, post-transcriptionally regulate mRNA via binding to the cap structure at the 5' end of mRNA or its 3' untranslated region (UTR) to generate a closed-loop structure. The 3' UTR of the transcript is also implicated in post-transcriptional regulation through an association with proteins such as CPEB, CPSF, GLD-2, PARN, and Dazl to modulate poly(A) tail length. RNA interfering is a new regulatory mechanism of the amount of mRNA in the mouse oocyte. This review summarizes information about post-transcriptional and post-translational regulation during mouse oocyte meiotic maturation.

• Journal of the Korean Data and Information Science Society
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• 제27권1호
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• pp.225-243
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• 2016

Thanks to recent advance of next generation sequencing techniques, RNA-seq enabled to have an unprecedented opportunity to identify transcript variants with isoform diversity and allelic imbalance (Anders et al., 2012) by different transcriptional rates. To date, it is well known that those features might be associated with the aberrant patterns of disease complexity such as tissue (Anders and Huber, 2010; Anders et al., 2012; Nariai et al., 2014) specific differential expression at isoform levels or tissue specific allelic imbalance in mal-functionality of disease processes, etc. Nevertheless, the knowledge of post-transcriptional modification and AI in transcriptomic and genomic areas has been little known in the traditional platforms due to the limitation of technology and insufficient resolution. We here stress the potential of isoform variability and allelic specific expression that are relevant to the abnormality of disease mechanisms in transcriptional genetic regulatory networks. In addition, we systematically review how robust Bayesian approaches in RNA-seq have been developed and utilized in this regard in the field.

• Molecules and Cells
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• 제41권5호
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• pp.381-389
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• 2018

ARF is a tumor suppressor protein that has a pivotal role in the prevention of cancer development through regulating cell proliferation, senescence, and apoptosis. As a factor that induces senescence, the role of ARF as a tumor suppressor is closely linked to the p53-MDM2 axis, which is a key process that restrains tumor formation. Thus, many cancer cells either lack a functional ARF or p53, which enables them to evade cell oncogenic stress-mediated cycle arrest, senescence, or apoptosis. In particular, the ARF gene is a frequent target of genetic and epigenetic alterations including promoter hyper-methylation or gene deletion. However, as many cancer cells still express ARF, pathways that negatively modulate transcriptional or post-translational regulation of ARF could be potentially important means for cancer cells to induce cellular proliferation. These recent findings of regulators affecting ARF protein stability along with its low levels in numerous human cancers indicate the significance of an ARF post-translational mechanism in cancers. Novel findings of regulators stimulating or suppressing ARF function would provide new therapeutic targets to manage cancer- and senescence-related diseases. In this review, we present the current knowledge on the regulation and alterations of ARF expression in human cancers, and indicate the importance of regulators of ARF as a prognostic marker and in potential therapeutic strategies.

• Journal of Applied Biological Chemistry
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• 제53권3호
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• pp.121-125
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• 2010

지난 10년간 분자 식물 일주기성에 대해 분자 생물학적, 생화학적인 연구가 많이 진행되었다. 본 연구에서는 식물의 Arabidopsis, rice 그리고 algae에서 지금까지 발표된 연구들을 종합하고 고찰해보려 했다. 그 결과, 아직까지도 주기성 대사의 모든 부분을 설명하기엔 부족한 부분이 많다는 것을 알수 있었다. 최근 주기성 단백질들의 전사후, 번역 그리고 번역후 변형과정에 대해 많은 연구자들이 관심을 갖기 시작했다. 이러한 부분에서 다량의 단백질을 한번에 볼 수 있는 2-DE gel electrophoresis와 MS/MS 기술이 절실히 요구된다고 할 수 있겠다.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.330.1-330.1
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• 2002

Arginine methylation is a common post-translation protein modification in eukaryotic cells. Protein-arginine N-methyltransferase transfer methyl groups from S-adenosyl-L-methionine to the guanidino group of arginine residues. However. The significant of this modification has been questionable. because it occurs rarely and is present at very low abundance. Recently, the discovery of two protein arginine methyltransferase, PRMT1 and CARM1, as cofactors required for responses to muclear Hormone receptors provided an indicationthat arginine methylationhave an important role in transcriptional regulation. (omitted)

• 한국식물학회:학술대회논문집
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• 한국식물학회 1987년도 식물생명공학 심포지움 논문집 Proceedings of Symposia on Plant Biotechnology
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• pp.283-307
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• 1987

Glycinin and $\beta$-conglycinin are the most abundant storage protein in soybean. These proteins are known to be synthesized predominantly during germination and cell expansion phase of seed development for short period, and synthesized not in other tissues. Genes encoding these storage proteins are useful system to study the mechanism of development stage and tissue specific gene expression in eukaryotes, especially plants, at the molecular level. The cDNA and genomic clones coding for glycinin have been isolated and regulation mechanism of the gene expression has been studied. Initially, development and tissue-specific expression of the glycinin gene is regulated at the level of transcription. Post-transcriptional processing is also responsible for delayed accumulation of the mRNA. Translational control of the storage protein gene has not been reported. Post-translational modification is another strategic point to regulate the expression of the gene. It is possible to identify positive and/or negative reguratory clements in vivo by producing transgenic plants agter gene manipulation. Elucidation of activation and repression mechanism of soybean storage protein genes will contribute to the understanding of the other plant and eukaryotic genes at molecular level.

• Reproductive and Developmental Biology
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• 제38권1호
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• pp.41-52
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• 2014

Embryonic genome activation (EGA) is a highly complex phenomenon that is controlled at various levels. New studies have ascertained some molecular mechanisms that control EGA in several species; it is apparent that these same mechanisms regulate EGA in all species. Protein phosphorylation, DNA methylation and histone modification regulate transcriptional activities, and mechanisms such as ubiquitination, SUMOylation and microRNAs post-transcriptionally regulate development. Each of these regulations is highly dynamic in the early embryo. A better understanding of these regulatory strategies can provide the possibility to improve the reproductive properties in mammals such as pigs, to develop methods of generating high-quality embryos in vitro, and to find markers for selecting developmentally competent embryos.

• Biomolecules & Therapeutics
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• 제15권2호
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• pp.78-82
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• 2007

The proto-oncogene protein DEK is a nuclear binding phosphoprotein that has been associated with various human diseases including leukemia. Histone acetylation is an important post-translational modification which plays important role in transcriptional regulation. Auto-acetylation of histone acetyltransferase PCAF results in increment of its HAT activity and facilitation of its nuclear localization. In this study, we report that DEK inhibits PCAF auto-acetylation through direct interaction. The C-terminal acidic domains of DEK are responsible for the interaction with PCAF. Using confocal microscopy, we have shown that nuclear localization of PCAF is severely inhibited by DEK. Taken together, our results suggest that DEK may be involved in various cellular signal transduction pathways accommodated by PCAF through the regulation of PCAF auto-acetylation.