Regulation and Functions of the p53 Protein

Its locus is particularly amplified in these noted tumours leading to the progression of these cancers, it can be suppressed by p53 (tumour/ proliferation suppressor) which represses the EZH2 promoter, resulting inhibition of cell proliferation and invasion (Bracken, 2003; Xiao, 2011).

In vitro: In lymphocytes, Cladribine caused accumulation of DNA strand breaks, subsequently activating the tumor suppressor p53. In MM1.S, RPMI8226 and U266 cells, Cladribine dose-dependently inhibited cell proliferation and survival [1].

TP53 is a 20kb long gene located on the small arm of chromosome 17 [18]. It is the first tumor suppressor gene to be identified and the most extensively studied [19, 20]. First described in 1979, this gene was first believed to be an oncogene, a cell growth promoter [19]. However, data form in-vivo studies performed years later provided convincing evidence supporting its tumor suppressive activity [18, 21].

In the book p53: The Gene That Cracked The Cancer Code by Sue Armstrong, they focus on statistics rather than a story. This book describes the change throughout time while focusing on the p53 gene. It talks about different genes that affect p53 and how cancer can happen.

The CDKN2A gene is responsible for a majority of melanomal families. The CDKN2A gene is responsible for 10% of families with two members that have melanoma and is responsible for 30-40% of families that have three members connected with melanoma. The linkage between the CDKN2A gene mutation and melanoma was found in 1994. (Aoude et al. 2015). The CDKN2A gene is located on chromosome 9p21. CDKN2A is used to help create two types of proteins, p16 and p14. Both of these proteins have functions that relate to regulating the cell cycle. They also function as tumor suppressants in the body. When the p16 and p14 proteins are being produced, they are transcribed on exons. An exon is a part of the gene that helps to create amino acids through coding (Exon). The process of transcription involves copying segments of DNA into RNA using enzymes. p16 and p14 are transcribed on different exons (1α and 1β) and use the same second and third exon when producing their amino acids. The amino acid created are different between the two proteins. The mutation of the CDKN2A gene occurs in the 1α exon affects the p16 protein during the transcription stage. Mutations can also occur in the 1β exon where both the p16 and p14 proteins would be affected. Affecting one

Women with mutations in the p53 gene also may be at increased risk of developing breast cancer. However, mutations of the p53 gene are rare, affecting an estimated 1 in 10,000 individuals (Athma et al., 1996 cited in McCain, 1997).

The function of YY1 in transcription is context-specific and requires interactions with many cellular factors. As a result, YY1 develops intracellular networks that allow it to induce multiple functions in transcriptional initiation, activation and repression, ultimately leading to the regulation of normal cell growth and survival. As a DNA binding protein, YY1 functions in the replication and regulation of the histone alpha complex, vital for proliferating cells[29].Overexpression of YY1 in tumor tissues exerts different clinical behavior in different tumor types. YY1 The loss of YY1 results in a significant increase in p53 levels. YY1, MDM-2 and p53 can form a ternary complex and YY1 is essential for optimal MDM2-p53 physical interactions in vivo, which is a prerequisite for MDM2 to be able to ubiquinate p53. Ubiquitination induces the translocation of p53 to the proteasome which leads to its

The normal function of the p53 gene is to bind to other genes like miRNA34a (which codes for p21)(3). P21 is a protein that acts as signal for the shut of DNA replication, so mutation in P53 causes no direct signal to the p21 gene and there is uncontrolled growth and proliferation.

To elaborate, exposure of cells to Istodax results in reduced cyclin D1 and c-Myc, followed by an increase in p53-independent p21 WAF1/Cip1 induction (VanderMolen, McCulloch, Pearce & Oberlies, 2011). The p21 induction leads to inhibition of cyclin-dependent kinase via the downregulation of cyclins, causing retinoblastoma (Rb) dephosphorylation and indirectly effecting E2F transcription activity, which results in early G1 phase cell cycle arrest (VanderMolen, McCulloch, Pearce & Oberlies,

Enzyme synthesis is regulated and controlled via regulatory proteins that are repressed or induced, repression is associated with anabolism while catabolism is seen with inducers. Another component is that of promoter and effector. The effector molecule is one that works with the repressor, altering the affinity for the operator in the controlling region of the gene (McClean 2017). The promoter is described as the binding site for the RNA polymerase (KhanAcademy). This regulation occurs at the transcriptional level (UW-Milwaukee, 2017).

The class Leu, Trp, Ade dropout plates (Table 2) showed that there are interactions between the Bub1B protein produced between 186 and 613 bp on the Bub1B1 gene and CDC20 protein, as shown in Figure 1. There are interactions between the Bub1B protein produced between 328 and 588 bp and BUB3 protein. There are interactions between the Bub1B protein produced between 588 and 1052 bp and Ppp2r5c protein. There are no interactions between the Bub1B and Zfp207

In both eukaryote and prokaryote, transcription is the first step for a gene to be expressed and also highly regulated process by several distinct steps. Therefore, misregulation of transcription caused by mutations in transcriptional regulatory sequences or factors can lead to variety of diseases. In order to start transcription process, multi-subunit RNA polymerase (RNAP) from both bacterial and eukaryotic cells require various factors. Some of them are regulatory sequence-specific DNA binding proteins (activators or repressors) that can specifically recognize and bind to DNA at the promoter. These factors are recruited specifically in stepwise to help RNAP along

The histone protein plays major role in interacting with other chemical groups which expose DNA and shield some sections.

It may be possible to correct an abnormality in a tumor suppressor gene such as P53 by inserting a copy of the wild-type gene; in fact, insertion of the wild-type P53 gene into P53-deficient tumor cells has been shown to result in the death of tumor cells (3). This has significant implications, since P53 alterations are the most common genetic abnormalities in human cancers. The over expression of an oncogene such as K-RAS can be blocked at the genetic level by integration of an antisense gene whose transcript binds specifically to the oncogene RNA, disabling its capacity to produce protein. Experiments in vitro and in vivo have demonstrated that when an antisense K-RAS vector is integrated into lung cancer cells that over express K-RAS their tumorigenicity is decreased (4).

The ccdB gene (see below) for negative selection (present in donor, destination, and supercoiled entry vectors)