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1.
Biochim Biophys Acta Gene Regul Mech ; 1866(3): 194960, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37467925

RESUMO

The transcription factor E2F1 participates in cell cycle control through transcriptional activation of genes that promote S-phase entry. E2F1 is also linked to the expression of proapoptotic genes, and the loss of E2F1 activity facilitates tumor progression by reducing cellular apoptosis. Phosphorylation controlled by protein kinases and phosphatases is the major posttranslational modification and regulates the cellular levels and transactivator function of E2F1. Here, we characterize the regulatory roles of serine-375 (S375), one of the major phosphorylation sites of E2F1. Cyclin-dependent kinases such as CDK8 phosphorylate at S375 of E2F1, which is dephosphorylated by protein phosphatase 2A (PP2A) containing the B55 regulatory subunit. The PP2A adapter protein IER5 binds to both PP2A/B55 and E2F1 and assists dephosphorylation at S375 by PP2A. S375-dephosphorylated E2F1 exhibits higher DNA-binding affinity than the phosphorylated form. Although the promoter regions of proapoptotic genes are less occupied by E2F1 in cells, an increase in S375-dephosphorylated E2F1 induces preferential binding of E2F1 to the proapoptotic gene promoters and their expression. Our data identify PP2A/B55-IER5 as a critical regulator of E2F1 and suggest that the phosphorylation state of E2F1 is an important determinant for the expression of proapoptotic genes.


Assuntos
Proteína Fosfatase 2 , Serina , Proteína Fosfatase 2/genética , Serina/genética , Serina/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Expressão Gênica , DNA/metabolismo
2.
Rev Sci Instrum ; 79(10): 10E909, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19044564

RESUMO

A simultaneous measurement of imploded core plasma and injection time of heating laser is conducted by using an x-ray framing camera (XFC). The experiments are performed using Gekko XII laser system for implosion of the deuterated polystyrene (CD) plastic shell target and Peta Watt (PW) laser system for heating. The time of PW laser injection is observed as the bright zone in the XFC image. The measured x-ray intensity profiles fit the Gaussian profiles well. The calculations of microchannel plate by using dynode model explain these broadened temporal profiles qualitatively. The peak position of fitted x-ray intensity profile is almost in agreement with the time when the high energy x ray is observed by x-ray streak camera. Moreover, the peak position is delayed corresponding to the delayed setting of PW laser injection time. From these results, it is concluded that we can estimate the heating laser injection time with resolution of the order of 10 ps by using XFC.

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