• BMB Reports
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• 제56권11호
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• pp.612-617
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• 2023

Pleiotropic regulator 1 (PLRG1), a highly conserved element in the spliceosome, can form a NineTeen Complex (NTC) with Prp19, SPF27, and CDC5L. This complex plays crucial roles in both pre-mRNA splicing and DNA repair processes. Here, we provide evidence that PLRG1 has a multifaceted impact on cancer cell proliferation. Comparing its expression levels in cancer and normal cells, we observed that PLRG1 was upregulated in various tumor tissues and cell lines. Knockdown of PLRG1 resulted in tumor-specific cell death. Depletion of PLRG1 had notable effects, including mitotic arrest, microtubule instability, endoplasmic reticulum (ER) stress, and accumulation of autophagy, ultimately culminating in apoptosis. Our results also demonstrated that PLRG1 downregulation contributed to DNA damage in cancer cells, which we confirmed through experimental validation as DNA repair impairment. Interestingly, when PLRG1 was decreased in normal cells, it induced G1 arrest as a self-protective mechanism, distinguishing it from effects observed in cancer cells. These results highlight multifaceted impacts of PLRG1 in cancer and underscore its potential as a novel anti-cancer strategy by selectively targeting cancer cells.

• Molecules and Cells
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• 제38권1호
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• pp.20-25
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• 2015

TGF-${\beta}$ regulates pleiotropic cellular responses including cell growth, differentiation, migration, apoptosis, extracellular matrix production, and many other biological processes. Although non-Smad signaling pathways are being increasingly reported to play many roles in TGF-${\beta}$-mediated biological processes, Smads, especially receptor-regulated Smads (R-Smads), still play a central mediatory role in TGF-${\beta}$ signaling for epithelial-mesenchymal transition. Thus, the biological activities of R-Smads are tightly regulated at multiple points. Inhibitory Smad (I-Smad also called Smad7) acts as a critical endogenous negative feedback regulator of Smad-signaling pathways by inhibiting R-Smad phosphorylation and by inducing activated type I TGF-${\beta}$ receptor degradation. Roles played by Smad7 in health and disease are being increasingly reported, but the molecular mechanisms that regulate Smad7 are not well understood. In this study, we show that E3 ubiquitin ligase Itch acts as a positive regulator of TGF-${\beta}$ signaling and of subsequent EMT-related gene expression. Interestingly, the Itch-mediated positive regulation of TGF-${\beta}$ signaling was found to be dependent on Smad7 ubiquitination and its subsequent degradation. Further study revealed Itch acts as an E3 ubiquitin ligase for Smad7 polyubiquitination, and thus, that Itch is an important regulator of Smad7 activity and a positive regulator of TGF-${\beta}$ signaling and of TGF-${\beta}$-mediated biological processes. Accordingly, the study uncovers a novel regulatory mechanism whereby Smad7 is controlled by Itch.

• 미생물학회지
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• 제51권1호
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• pp.39-47
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• 2015

방선균이 생산하는 이차대사산물은 자기조절인자(${\gamma}$-butyrolactone autoregulator)라고 불리는 저분자의 신호전달물질과 이에 특이적으로 결합하는 autoregulator receptor protein의 상호작용에 의해 조절되는 것으로 알려져 있다. 그러므로 non-host에 autoregulator receptor 혹은 pleiotropic regulator의 발현은 이차대사산물 혹은 새로운 대사화합물의 효율적인 생산을 유도할 것으로 기대된다. 희소방선균 Saccharopolyspora erythreae으로부터 receptor (seaR) 유전자의 기능을 연구하기 위해 다른 속의 균주인 Streptomyces coelicolor A3(2)로 seaR 유전자를 삽입하여 형질전환하였다. S. coelicolor A3(2)의 형질전환은 oriT, attP, $ermEp^*$과 seaR gene 단편을 가지고 있는 ${\Phi}C31$ 유래의 integration vector인 pEV615 (6.6 kb)를 이용하여 Escherichia coli ET12567/pUZ8002를 DNA 공여체로 이용한 접합전달법을 사용하여 확립하였다. seaR 유전자의 삽입 유무는 PCR방법으로 확인하였고, seaR 유전자의 전사 발현은 RT-PCR방법으로 확인하였다. S. coelicolor A3(2)의 경우 표현형 microarray 실험을 통하여 seaR 유전자의 발현에 따른 표현형의 변화를 확인하였다. 특히, 표현형 microarray 실험에 나타난 tetracycline 항생제 기질에 대하여 wild type이 transformant에 비해 빠르게 성장하는 것은 항균제 감수성 검사와 일치하였다. 이는 tetracycline 생합성 유전자 및 내성 유전자의 발현 억제에 따른 변화라고 예상할 수 있으며 이를 위하여 tetracycline 생합성 관련 유전자 및 내성 유전자의 발현 패턴 분석등과 같은 분자 수준에서의 연구가 필요할 것으로 생각된다.