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Federal government ykn often end in. The site is secure. As a transcription factor, Yin Yang 1 YY1 regulates the transcription of a dazzling list of genes and the number of its targets still mounts. Recent studies revealed that YY1 possesses functions independent of its DNA binding activity and its regulatory role in tumorigenesis has started to emerge.
YY1 was discovered as a transcription factor and its transcriptional activity can be converted from a repressor to an activator by viral oncoprotein E1A. YY1 has been reported to modulate a mounting list of genes, many of which are downliad players in different signaling pathways regulating cancer development and progression, such as c-myc, c-fos, ERBB2, E1A and p To date, most published data have demonstrated the activities of YY1 as a transcription посмотреть еще. YY1 can either activate or repress gene expression, depending on the cofactors that it recruits.
Despite the well-established regulation of YY1 as a transcription factor, several reports, including ours, have demonstrated the role of YY1 as a transcription cofactor and its activity independent of its DNA binding. In our recent study, we observed YY1-dependent expression of prostatespecific antigen PSA in prostate cancer cells.
Therefore, instead of directly acting as feee transcription factor, YY1 plays a role of a cofactor and its DNA binding activity is dispensable in mediating PSA expression. The domain mapping studies indicate that the N-terminal of YY1 possesses transcriptional activation activity, and the N-terminal and middle region recruit many proteins with chromatin remodeling functions.
This is not the first observation of YY1 exhibiting activity independent of its DNA binding affinity. Importantly, this effect of YY1 on p53 could be visualized in a reconstituted ubiquitination system in vitro. The full length affinity designer yin yang free download YY1 protein has never been crystallized for structure analysis, except for the cocrystal study of its zinc finger region with the adeno-associated virus P5 promoter.
However, the amino acid composition of YY1 reveals some of its potential structural features. YY1 protein has two acidic regions at the N-terminal.
The afcinity charge of histidines may be altered with slight pH changes in the microenvironment. Therefore, the N-terminal of YY1 affinity designer yin yang free download employ affiniity force to interact with different proteins, especially those with positive charges, such as histones.
Between residues tothere are four clusters of three- to five-runs of glycines that provide large flexibility to this region, which interacts with several proteins, including affinity designer yin yang free download, HDACs, c-Myc, p53 and p14 ARF reviewed in affinity designer yin yang free download.
Overall, these features may determine the potential of YY1 as a scaffold protein that recruits other transcription regulators to mediate gene expression when its C-terminal binds to either DNA or other transcription factors.
YY1 interacts with a number of protein modifiers that mediate various posttranslational modifications. Especially, when a particular protein modifier binds to YY1, posttranslational modifications may occur to both продолжить чтение and other recruited cofactors on a target promoter to modulate their functions. This interplay between the recruitment and modification will therefore determine the affinitj status of the regulated genes.
Affinity designer yin yang free download addition, Mdm2 can cause histone ubiquitination and establishes transcriptional repression. When YY1 acts as a transcription coactivator in AR-mediated PSA gene expression, it is likely that YY1 affinity designer yin yang free download other coactivators that are yet to be identified to promote transcription Fig.
It is noteworthy that, as a cofactor, the cellular levels of YY1 may determine the expression status of a target gene. Therefore, while a medium increase of YY1 stimulates AR-mediated transcription, further increases of YY1 can compromise this activation. Schematic models of YY1 regulated gene expression. YY1 has been suggested as a regulatory protein, a potential therapeutic target and a prognostic marker of cancers based on its aberrant expression in tumors and free properties of its target genes and interacting proteins.
Mechanistically, YY1 negatively regulates the expression of both Fas and the death receptor 5 DR5and consequently endows prostate cancer cells with resistance to Fas-induced or TRAIL-induced apoptosis. Consistently, in a tissue microarray study, they observed that elevated YY1 expression correlates with higher morphologic grades or malignant histological phenotypes in prostate cancer samples from patients. Deesigner, in the absence of androgen, we observed a modest activation by Afinity on AR-dependent designeer of the PSA promoter, 6 suggesting that, as a coactivator, overexpressed YY1 may be an essential regulator to the AR-signaling pathway in androgen independent prostate cancer.
Prostate cancer desiger a major public health problem among men of many countries. While locally confined prostate tumors can be treated by surgery and radiation therapy, advanced and relapsed prostate cancers are primarily handled by inhibiting the androgen signaling pathway. This can be typically achieved by androgen deprivation therapy including castration and administration of androgen antagonists. However, despite these therapies of androgen withdrawal, prostate cancer unavoidably progresses to the androgen-independent state.
Even at low androgen levels, androgen-responsive genes in these tumors restore their affinity designer yin yang free download nearly to the pre-treatment levels.
In нажмите для деталей, such prostate cancers retain high expression levels of AR and are still AR-dependent. The aberrantly activated AR-signaling pathway in prostate cancer can be caused by different deregulations, including AR overexpression, AR mutation, increased sensitivity of AR to low androgen levels and ligand-independent AR activation. Given the fact that many coactivators and corepressors interact with YY1, specific agonists or antagonists to these proteins can be designed and tested, and molecular agents, such as peptide inhibitors, can be used to attenuate AR activity.
These studies can affinity designer yin yang free download lead to the development of new therapeutic strategies that are urgently needed to treat the fatal, advanced prostate cancer. We thank Ms. Published online May Author information Article notes Copyright and License information Disclaimer. Corresponding author. Correspondence to: Guangchao Sui; Email: ude. Abstract As a transcription factor, Yin Yang 1 YY1 regulates the transcription of a dazzling list of genes and the desigber of its targets still mounts.
Key words: Affinity designer yin yang free download Перейти на страницу 1, transcription factor, coactivator, protein modification, androgen receptor, prostate cancer. Open in a separate window. Figure 1. YY1: Involvement in Prostate Cancer YY1 has been suggested as a regulatory protein, a potential therapeutic target and a prognostic marker of cancers based on its aberrant expression in tumors and the properties of its target genes and interacting proteins.
Acknowledgements We thank Ms. Abbreviations YY1 Yin Yang 1. References 1. Targeted disruption of mouse Yin Yang 1 transcription factor results in peri-implantation lethality. Mol Cell Biol. Sui G. Mol Cell Pharmacol. Transcription factor YY1: structure, function and therapeutic implications in cancer biology.
Nucleic Acids Res. Yin Yang 1 regulates the transcriptional activity of androgen receptor. Thomas MJ, Seto E. Unlocking the mechanisms of transcription factor YY1: are chromatin modifying enzymes the key? J Biol Chem. Yin Yang 1 is a negative regulator of p YY1 inhibits the activation of the p53 tumor suppressor in response to genotoxic stress. Circ Res. J Cell Sci. Rizkallah R, Hurt MM. Regulation of the transcription factor YY1 in mitosis through phosphorylation of its DNA-binding domain.
Mol Biol Cell. Cocrystal structure of YY1 bound to the adenoassociated virus P5 initiator. Genes Dev. Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator RPD3. Основываясь на этих данных Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation.
Targeted recruitment of a histone H4-specific methyltransferase by the transcription factor YY1. Minsky N, Oren M. Mol Cell. Androgen receptor coregulators and their involvement in the development and progression of prostate cancer.
Int J Cancer. Bode AM, Dong Z. Post-translational modification of p53 in tumorigenesis. Nat Rev Cancer. Gill G, Ptashne M. Negative effect of the transcriptional activator GAL4. The involvement of the transcription factor Yin Yang 1 in cancer development and progression. Cell Cycle. Zaravinos A, Spandidos DA.
Yin yang 1 expression in human deskgner. Expression of transcription перейти Yin Yang 1 in prostate cancer. Int J Oncol. Failure of hormone therapy in prostate cancer involves systematic restoration of androgen responsive genes and activation of rapamycin sensitive signaling. Contribution of the androgen receptor to prostate cancer predisposition and progression.
Cancer Metastasis Rev. Regulation of androgen receptor signaling in prostate affinity designer yin yang free download.