• 생명과학회지
• /
• 제19권3호
• /
• pp.317-321
• /
• 2009

다운증후군은 추가적으로 존재하는 인간염색체 21번에 위치한 유전자의 과발현으로 발병한다. 다운증후군 환자에서 보이는 여러 증상들 중 학습과 기억능력 저하와 같은 뇌기능 저하는 다운증후군 환자가 독립적인 생활을 영위하는데 가장 큰 걸림돌이 된다. 인간염색체 21번에 위치하는 Dyrk1A는 신경발달에 중요한 역할을 하는 단백질로 Dyrk1A를 과발현 하는 형질전환 생쥐에서 심각한 해마 의존적 학습과 기억 장애가 보고되었다. 본 연구에서는 인간 Dyrk1A를 과발현 하는 형질전환 생쥐와 RNA interference (RNAi) 방법을 이용하여 endogenous mouse Dyrk1A의 발현은 정상적으로 유지하면서 exogenous human Dyrk1A 발현은 특이적으로 저해함으로써 인간 Dyrk1A 과발현에 의한 학습과 기억 능력저하를 회복시킬 수 있는지 동물모델에서 검증하기 위한 첫 단계로 인간 Dyrk1A 특이적 lentiviral short hairpin RNA (shRNA)를 발굴하였다. 발굴된 shRNA를 이용한 형질전환 모델생쥐에서의 증상의 회복 가능성 검증은 다운증후군의 뇌기능저하 치료제 개발에 중요한 정보를 제공할 것이다.

• BMB Reports
• /
• 제56권11호
• /
• pp.584-593
• /
• 2023

Hypoxia, a widespread occurrence observed in various malignant tumors, results from rapid tumor growth that outpaces the oxygen supply. Tumor hypoxia precipitates several effects on tumor biology; these include activating angiogenesis, intensifying invasiveness, enhancing the survival of tumor cells, suppressing anti-tumor immunity, and fostering resistance to therapy. Aligned with the findings that correlate CMGC kinases with the regulation of Hypoxia-Inducible Factor (HIF), a pivotal modulator, reports also indicate that hypoxia governs the activity of CMGC kinases, including DYRK1 kinases. Prolyl hydroxylation of DYRK1 kinases by PHD1 constitutes a novel mechanism of kinase maturation and activation. This modification "primes" DYRK1 kinases for subsequent tyrosine autophosphorylation, a vital step in their activation cascade. This mechanism adds a layer of intricacy to comprehending the regulation of CMGC kinases, and underscores the complex interplay between distinct post-translational modifications in harmonizing precise kinase activity. Overall, hypoxia assumes a substantial role in cancer progression, influencing diverse aspects of tumor biology that include angiogenesis, invasiveness, cell survival, and resistance to treatment. CMGC kinases are deeply entwined in its regulation. To fathom the molecular mechanisms underpinning hypoxia's impact on cancer cells, comprehending how hypoxia and prolyl hydroxylation govern the activity of CMGC kinases, including DYRK1 kinases, becomes imperative. This insight may pave the way for pioneering therapeutic approaches that target the hypoxic tumor microenvironment and its associated challenges.

• BMB Reports
• /
• 제42권1호
• /
• pp.6-15
• /
• 2009

The most common genetic disorder Down syndrome (DS) displays various developmental defects including mental retardation, learning and memory deficit, the early onset of Alzheimer's disease (AD), congenital heart disease, and craniofacial abnormalities. Those characteristics result from the extra-genes located in the specific region called 'Down syndrome critical region (DSCR)' in human chromosome 21. In this review, we summarized the recent findings of the DYRK1A and RCAN1 genes, which are located on DSCR and thought to be closely associated with the typical features of DS patients, and their implication to the pathogenesis of neural defects in DS. DYRK1A phosphorylates several transcriptional factors, such as CREB and NFAT, endocytic complex proteins, and AD-linked gene products. Meanwhile, RCAN1 is an endogenous inhibitor of calcineurin A, and its unbalanced activity is thought to cause major neuronal and/or non-neuronal malfunction in DS and AD. Interestingly, they both contribute to the learning and memory deficit, altered synaptic plasticity, impaired cell cycle regulation, and AD-like neuropathology in DS. By understanding their biochemical, functional and physiological roles, we hope to get important molecular basis of DS pathology, which would consequently lead to the basis to develop the possible therapeutic tools for the neural defects in DS.

• Asian-Australasian Journal of Animal Sciences
• /
• 제29권12호
• /
• pp.1675-1681
• /
• 2016

The aim of this study was to detect positional candidate genes located within the support interval (SI) regions based on the results of red blood cell, mean corpuscular volume (MCV), and mean corpuscular hemoglobin quantitative trait locus (QTL) in Sus scrofa chromosome 13, and to verify the correlation between specific single-nucleotide polymorphisms (SNPs) located in the exonic region of the positional candidate gene and the three genetic traits. The flanking markers of the three QTL SI regions are SW38 and S0215. Within the QTL SI regions, 44 genes were located, and runt-related transcription factor 1, dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A), and potassium inwardly-rectifying channel, subfamily J, member 15 KCNJ15-which are reported to be related to the hematological traits and clinical features of Down syndrome-were selected as positional candidate genes. The ten SNPs located in the exonic region of the three genes were detected by next generation sequencing. A total of 1,232 pigs of an $F_2$ resource population between Landrace and Korean native pigs were genotyped. To investigate the effects of the three genes on each genotype, a mixed-effect model which is the considering family structure model was used to evaluate the associations between the SNPs and three genetic traits in the $F_2$ intercross population. Among them, the MCV level was highly significant (nominal $p=9.8{\times}10^{-9}$) in association with the DYRK1A-SNP1 (c.2989 G$F_2$ intercross, our approach has limited power to distinguish one particular positional candidate gene from a QTL region.

• 한국생명과학회:학술대회논문집
• /
• 한국생명과학회 2007년도 제48회 학술심포지움 및 추계국제학술대회
• /
• pp.83.2-83.2
• /
• 2007

See Full Text

• 통합자연과학논문집
• /
• 제6권4호
• /
• pp.234-243
• /
• 2013

N-terminal kinase-like (NTKL) protein was initially identified as a protein binding to protein kinase B (PKB, also known as Akt). Though NTKL-BP1 (NTKL-binding protein 1) has been identified as an NTKL binding protein, its functions related to binding have not yet been elucidated. Here, a new alternative spliced variant of NTKL and its association with integrin ${\beta}1$ is described, in addition to the kinase activity of NTKL and its substrate candidates. Although the phosphorylation of the candidates must be further confirmed using other experimental methods, the observation that NTKL can phosphorylate ROCK1, DYRK3, and MST1 indicates that NTKL may act as a signaling protein to regulate actin assembly, cell migration, cell growth, and to facilitate differentiation and development in an integrin-associated manner.

• 한국균학회소식:학술대회논문집
• /
• 한국균학회 2014년도 추계학술대회 및 정기총회
• /
• pp.43-43
• /
• 2014

The rice blast disease caused by of Magnaporthe oryzae is one of the most destructive diseases of rice. By the microarray analysis, we profiled expression changes of genes during conidiation and found out many putative genes that are up-regulated. Among those, we first selected MGG_06399 encoding a dual-specificity tyrosine-regulated protein kinase (DYRK), homologous to YAK1 in yeast. To investigate functional roles of MoYAK1, We made ${\Delta}Moyak1$ mutants by homology dependent gene replacement. The deletion mutant showed a remarkable reduction in conidiation and produced abnormally shaped conidia smaller than those of wild type. The conidia form ${\Delta}Moyak1$ were able to develop a germ tube, but failed to form apppressoria on a hydrophobic coverslip. The ${\Delta}Moyak1$ formed appressria on a hydrophobic cover slip when exogenous cAMP was induced, but the appressoria shape was abnormal. The ${\Delta}Moyak1$ also formed appressoria abberent in shape on onion epidermis and rice sheaths and failed to penetrate the surface of the plants. These data indicate that MoYAK1 is associated with cAMP/PKA pathway and important for conidiation, appressorial formation and pathogenic development in Magnaporthe oryzae. Detailed characterization of MoYAK1 will be presented.