亚洲色综合导航,欧美性爱H版A片,激情导航,亚洲干综合,日本外道魂在线视频,avtt天堂网中文

CCNE1和E2F1部分抑制剪接抑制素 A 治療引起的 G1 期阻滯

CCNE1 and E2F1 Partially Suppress G1 Phase Arrest Caused by Spliceostatin A Treatment

The potent splicing inhibitor spliceostatin A (SSA) inhibits cell cycle progression at the G1 and G2/M phases. We previously reported that upregulation of the p27 cyclin-dependent kinase inhibitor encoded by CDKN1B and its C-terminal truncated form, namely p27*, which is translated from CDKN1B pre-mRNA, is one of the causes of G1 phase arrest caused by SSA treatment. However, the detailed molecular mechanism underlying G1 phase arrest caused by SSA treatment remains to be elucidated. In this study, we found that SSA treatment caused the downregulation of cell cycle regulators, including CCNE1, CCNE2, and E2F1, at both the mRNA and protein levels. We also found that transcription elongation of the genes was deficient in SSA-treated cells. The overexpression of CCNE1 and E2F1 in combination with CDKN1B knockout partially suppressed G1 phase arrest caused by SSA treatment. These results suggest that the downregulation of CCNE1 and E2F1 contribute to the G1 phase arrest induced by SSA treatment, although they do not exclude the involvement of other factors in SSA-induced G1 phase arrest.

有效的剪接抑制劑 spliceostatin A (SSA) 抑制 G1 和 G2/M 期的細(xì)胞周期進(jìn)程。我們之前報(bào)道過由CDKN1B編碼的 p27 細(xì)胞周期蛋白依賴性激酶抑制劑及其 C 端截短形式，即從CDKN1B前體 mRNA翻譯而來的 p27* 的上調(diào)是 SSA 治療引起的 G1 期停滯的原因之一. 然而，由 SSA 治療引起的 G1 期停滯的詳細(xì)分子機(jī)制仍有待闡明。在這項(xiàng)研究中，我們發(fā)現(xiàn)，SSA治療導(dǎo)致細(xì)胞周期調(diào)控的下調(diào)，包括CCNE1，CCNE2和E2F1, 在 mRNA 和蛋白質(zhì)水平。我們還發(fā)現(xiàn) SSA 處理的細(xì)胞中基因的轉(zhuǎn)錄延長是有缺陷的。的過表達(dá)CCNE1和E2F1與組合CDKN1B敲除部分抑制引起的SSA治療G1期阻滯。這些結(jié)果表明CCNE1和E2F1的下調(diào)有助于 SSA 治療誘導(dǎo)的 G1 期停滯，盡管它們不排除其他因素參與 SSA 誘導(dǎo)的 G1 期停滯。

T75細(xì)胞培養(yǎng)瓶

Cell cycle progression is closely controlled by cell cycle regulators. Among these reg‐ulators, cyclin family proteins and cyclin‐dependent kinases (CDKs) promote cell cycleprogression [1,2]. In G1/S phase transition, cyclin E1 and cyclin E2 (collectively known ascyclin E), along with Cdk2, are the key players that phosphorylate a variety of substrates[3–6]. Rb is a substrate of the cyclin E–Cdk2 complex; it binds the E2F1 transcription factorand represses the transcriptional activity of E2F1 [7,8]. After phosphorylation by cyclin E–Cdk2, Rb releases E2F1, and E2F1, in turn, activates the transcription of numerous genesthat drive the initiation of the S phase. The genes encoding cyclin E are controlled by E2F1,and thus the cyclin E–Cdk2 complex and E2F1 form a positive feedback loop that pro‐motes G1/S phase transition [3,4,6,9]. The cyclin E–Cdk2 complex also phosphorylatesSmad3, CBP/p300, and NPAT, leading to cell cycle progression [10–13]. Conversely, CDKinhibitors repress cell cycle progression by inhibiting the kinase activity of CDKs [2,9].p27 is one of the CDK inhibitors that control G1/S phase transition [9,14,15]. It binds toand inhibits the cyclin E–Cdk2 complex to block cell cycle progression at the G1 phase.The cyclin E–Cdk2 complex negatively regulates p27 through phosphorylation of p27,which induces ubiquitination and proteasomal degradation of p27 [16–18]. Collectively,these factors regulate G1/S phase transition in a coordinated manner.、

三角細(xì)胞培養(yǎng)搖瓶500ml

細(xì)胞周期的進(jìn)展受到細(xì)胞周期調(diào)節(jié)因子的密切控制。其中注冊(cè)檢測(cè)細(xì)胞周期蛋白家族蛋白和細(xì)胞周期蛋白依賴激酶(CDKs)促進(jìn)細(xì)胞周期進(jìn)展[1,2]。在G1/S相變中，cyclin E1和cyclin E2(統(tǒng)稱為cyclin E)和Cdk2是磷酸化多種底物的關(guān)鍵分子(3 - 6)。Rb是cyclin E-Cdk2復(fù)合物的底物;它與E2F1轉(zhuǎn)錄因子結(jié)合并抑制E2F1的轉(zhuǎn)錄活性[7,8]。經(jīng)cyclin E -磷酸化后Cdk2、Rb釋放E2F1，而E2F1反過來激活許多基因的轉(zhuǎn)錄驅(qū)動(dòng)S階段的開始。編碼周期素E的基因由E2F1控制，因此，cyclin E-Cdk2復(fù)合物和E2F1形成了一個(gè)正反饋回路motes G1/S相變[3,4,6,9]。周期蛋白E-Cdk2復(fù)合物也磷酸化Smad3、CBP/p300和NPAT導(dǎo)致細(xì)胞周期進(jìn)展[10-13]。相反,CDK抑制劑通過抑制CDKs的激酶活性來抑制細(xì)胞周期進(jìn)程[2,9]。p27是控制G1/S相變的CDK抑制劑之一[9,14,15]。并抑制cyclin E-Cdk2復(fù)合物在G1期阻斷細(xì)胞周期進(jìn)程。cyclin E-Cdk2復(fù)合物通過p27的磷酸化負(fù)調(diào)控p27，誘導(dǎo)p27的泛素化和蛋白酶體降解[16-18]?？偟膩碚f,這些因素協(xié)同調(diào)節(jié)G1/S相變。

來源：MDPI https://www.mdpi.com/1422-0067/22/21/11623