Year-end Sale % OFF 
Abstract
Transactivation of p21 (cyclin-dependent kinase inhibitor 1A, CDKN1A) is closely related to the recruitment of transcription cofactors at the p53 responsive elements (p53REs) in its promoter region. Human chromatin remodeling enzyme INO80 can be recruited to the p53REs of p21 promoter and negatively regulates p21. As one of the key subunits of the INO80 complex, YY1 has also been confirmed to bind to the p53RE sites of p21 promoter. Importantly, YY1 was recently reported to be bound and stabilized by BCCIP (BRCA2 and CDKN1A-interacting protein). Therefore, we hypothesized that the YY1/BCCIP complex plays an important role in regulating the transactivation of p21. Here we present evidence that the YY1/BCCIP complex coordinatively regulates p53RE-mediated p21 transactivation. We first confirmed the cross-interaction between YY1, BCCIP, and p53, suggesting an intrinsic link between three proteins in the regulation of p21 transcription. In dual luciferase assays, YY1 inhibited p53RE-mediated luciferase activity, whereas BCCIP revealed the opposite effect. More interestingly, the region 146–270 amino acids of YY1, which bound to BCCIP, increased p53-mediated luciferase activity, indicating the complexity of the YY1/BCCIP complex in co-regulating p21 transcription. Further in-depth research confirmed the co-occupancy of YY1/BCCIP with p53 at the p53RE-proximal region of p21. Lentiviral-mediated knockdown of BCCIP inhibited the recruitment of p53 and YY1 at the p53RE proximal region of p21; however, this phenomenon was reversed by expressing exogenous YY1, suggesting the collaborative regulation of YY1/BCCIP complex in p53RE-mediated p21 transcription. These data provide new insights into the transcriptional regulation of p21 by the YY1/BCCIP complex.
Highlights
The TP53 gene encodes the p53 protein that plays critical role in tumor prevention by taking control of a wide variety of cellular responses and the expression of multiple genes that regulates stress signal pathways [1]
We previously showed that p21 expression is negatively regulated by the INO80 chromatin remodeling complex through binding to the p53 responsive elements (p53REs) in the p21 promoter region [9]
Stabilization of BCCIP on p53 Was Regulated by YY1 in HCT116 (p53+/+) Cells
Summary
The TP53 gene encodes the p53 protein that plays critical role in tumor prevention by taking control of a wide variety of cellular responses and the expression of multiple genes that regulates stress signal pathways [1]. The DNA binding domain is well structured In contrast both the N- and C-terminal domains are intrinsically disordered [4,5]. These different domains can be bound by different proteins, demonstrating the diversity of the biological functions of p53. The co-activator p300-dependent acetylation of the C-terminal domain of p53 can stabilizes the protein by preventing Mdm2-mediated degradation [6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
