Regulation And Functions Of The P53 Protein

1189 words - 5 pages

p53 gene, also known as tumor protein 53 (TP53), encodes for a tumor suppressor protein which regulates the cell cycle and apoptosis. The p53 protein has been described as the guardian of the genome (1) because of its role in preventing genetic mutation. It belongs to a protein family which includes p53, p63 and p73 and these are structurally and functionally related to each other. However, p53 seems to have evolved as a tumor suppressor in higher organisms, while p63 and p73 play a role in normal developmental biology (2).

Structure of p53
P53 functions primarily as a transcription factor, and is biologically active as a homo-tetramer comprising of 4 X 393 amino acid residues. Each monomer ...view middle of the document...

It performs these functions by activating the transcription of various genes like p21 (growth arrest), p53R2 (DNA repair), Bax, Apaf-1 and PUMA (apoptosis) etc. The functions of p53 target genes are diverse, corresponding to the p53’s multifaceted regulatory activity (2).

Regulation of p53
Various stressors induce post-translational modifications and force p53 to be activated as a transcription regulator in these cells. This begins with phosphorylation of the N-terminal by protein kinases (like p38kinase, JNK1/2) at various serine residues, which allows binding of several transcriptional coactivators like p300 (3). These coactivators then acetylate the carboxyl terminus domain of p53, which exposes the DNA binding domain allowing it to induce a transcriptional activity.
Phosphorylation of p53 is a critical step as it also prevents its degradation by ubiquitination. In the absence of stress, p53 levels are maintained low through continuous degradation, by an auto-regulatory process. p53 activates the transcription of a protein MDM2, which is a E3 ubiquitin ligase. MDM2 covalently attaches ubiquitin to p53 and marks it for degradation by proteasomes(4). This is however reversible, by proteases like USP7 (5).

Therapeutic applications of p53 in Cancer
Therapeutic intervention to restore p53 function in tumors has been mainly focused on targeting destabilized oncogenic p53 mutant. Most mutations cause destabilization and unfolding of p53 structure. Hence, drug molecules are being designed to stabilize the protein at physiological temperatures and restore its transcriptional functionality (6).
Another approach is to target the negative modulators of p53 like MDM2. Many cancers with wild type p53 show increased expression of MDM2 which results in increased degradation and suppression of p53 function (6). Disruption of p53-MDM2 interaction by small molecules should result in restoration of p53 functionality in these cancers.

Role of p53 in other pathological processes
In contrast to the detrimental effects of loss in p53 function in cancer, activation of p53 by stress signals can also lead to several pathologies. For example, p53-mediated apoptosis can be related to the side effects associated with chemotherapies and radiation therapies (7). p53-mediated neuronal apoptosis also contributes to the pathologies seen in various neuro-degenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases (8, 9, 10, 11).
Studies in diabetic mice indicate a p53-dependent senescence response in fat cells, which resulted in insulin resistance in obese mice (12). Also, inhibition of p53 function restores...

Find Another Essay On Regulation and functions of the p53 protein

The Global Financial Crisis and The Regulation of Investment Banks

1271 words - 6 pages Lessons of GFC for the regulation of Investment Bank Investment Banks enable individuals, institutions such companies, governments to raise capital by offering underwriting services or working as an agents of the client in offering securities or in both roles. Investments banks play a very important role in stimulating investments in the United States both from individuals and corporate. The global financial environment has over the last

The Role and Functions of Law

841 words - 3 pages Running head: ROLE AND FUNCTIONS OF LAW PAGE \* MERGEFORMAT 1 ROLE AND FUNCTIONS OF LAW PAGE \* MERGEFORMAT 5 Role and Functions of LawJames TeagueLAW421February 03, 2014Teresa AndersonRole and Functions of LawThroughout history law has been defined many different ways. A generally accepted generic definition of the law is a body of rules of action or conduct prescribed by controlling authority, and having legal binding force (College, 2011

The Importance of Emotional Self-Regulation and Secure Attachments

2384 words - 10 pages “Growth of self-regulation is a cornerstone of early childhood development and is visible in all areas of behavior” (Shonkoff & Phillips, 2000) Throughout the course of a person’s life, they will face many situations where self-regulation of the emotions is needed to make decisions that can determine a positive outcome of a given situation. Most adult are able to think about the consequences of their actions before a situation gets out of

Sikhism: Structures and Functions of the Gurdwara

2889 words - 12 pages back to the Gurdwara. Because of the nature of the duty, it is performed jointly by the husband and the wife. They share this responsibility depending upon the nature and time of the duty.Sikhs are expected to go to a Gurdwara always in a formal and respectful dress wear. Whatever the modern trend of wearing clothes, both boys and girls when in their teens, should attend Gurdwara or formal functions in formal clothes.Bowing before Guru Granth

Interracial Intimacy: The Regulation of Race and Romance

1546 words - 6 pages Interracial Intimacy: The Regulation of Race and Romance Works Cited Missing Regardless of our social rhetoric of color-blindness, when it comes to choosing a spouse we seem to be remarkably aware of color, at least we were legally for more than 200 years and despite legal permission, society still exacts a social opinion on the matter. Law professor Rachel Moran examines this issue in Interracial Intimacy: The Regulation of Race and

The Definition and Functions of Smart Gird

996 words - 4 pages A smart grid (SG) is an intelligent electricity network that integrates the actions of all users that are connected to it and make use of advanced information, control, and communication technologies in order to efficiently deliver sustainable, economic and secure electricity supplies [1]. The high-speed, bi-directional, real-time, and integrated communications system is the foundation of SG [2]. In addition to counting and pricing in smart

Roles and Functions of the Nurse

1290 words - 6 pages 1.1 Jane has been allocated a bed on my ward. I introduce myself to her and make sure she knows why she has been admitted and inform her of support available.2.1 using the ropers model; activities of living (Fundamentals of Nursing made Incredibly Easy Pg. 16) My generic skills as a nurse, would be ensuring Jane is settled and comfortable and ensuring the safety and privacy of the environment. Informing her of the imminent steps we will be

Role of the United States Constitution and Business Regulation

736 words - 3 pages University of PhoenixThe role of the United States Constitution in business falls under Article I, Clause 3, Commerce Power, Power to Regulate Commerce. The role will be discussed in this paper along with a current example from today's world. The example will show how Constitutional rights can affect business and how our legal system will be used to protect those rights.The Commerce ClauseCongress has the sole power to govern commerce or

Translation and Protein Synthesis- the role of various RNA and the process of synthesis

709 words - 3 pages coding of m-RNA from a DNA molecule to the release of a protein chain that then has many possible functions and destinations.References:BIOLOGY by Neil A. Campbell, Fourth EditionBiology: The Unity and Diversity of Life by Cecie Starr and Ralph Taggart, Fifth Edition

Impact of the Presence of Protein Aggregates

1822 words - 8 pages In the last decade, protein aggregation, protein aggregation has moved beyond being a mostly ignored area of protein chemistry to become a key topic in biomedicine and biotechnology [1]. Several are the reasons for the increasing interest on the molecular mechanisms underlying protein aggregation. First, the presence of protein aggregates in tissues is hallmark of more than 40 different human disorders, from neurodegenerative diseases such as

Is Whey Protein the way to go?-Research Paper on the benefits and drawbacks of using whey protein for weight training

3045 words - 12 pages Is Whey Protein the way to go?IntroductionWhey protein has become one of the most popular and safe ways in achieving "optimal health". Whey protein is also used to gain an "edge" is sport related activities along with bodybuilding. But where exactly does whey protein come from? Whey protein is a co-product of cheese, which is naturally in cow's milk. (Vardhanabhuti 1999) However, whey protein is not the only protein available from cow's milk

Similar Essays

Runx2 Binding Protein And The Regulation Of Osteogenesis

1964 words - 8 pages Runx2 Binding Protein and the Regulation of Osteogenesis In the developmental process of osteogenesis, bone is formed, laid down, and repaired in a highly regulated process (Wu et al., 2014a). This organized formation of bone tissue is controlled by the nucleic acid binding protein Runx2 (Wu et al., 2014a). Runx2 regulates transcriptional mechanisms in osteoblast cells, or bone forming cells, that are vital to the formation of bone tissue

Effects Of Gene P53 The Tumor Repressor

917 words - 4 pages "Induction of Cytotoxic T Lymphocytes and Antitumor Immunity with DNA Vaccines Expressing Single T Cell Epitopes," by Frank Ciernik, Jay A. Berzofsky, and David P. Carbone explores the uses of the gene gun and how it can induce both humoral and cellular immunity. The paper specifically explores the effects of p53, a tumor repressor which gets its name from its molecular weight( p53 is a protein that has a molecular weight of 53). It is

Neurons And The Mecp2 Protein Essay

1307 words - 6 pages Syndrome. DNA methylation prevents the transcription factors from binding, with MECP2 acting as a repressor. But with mutated MECP2 in affected individuals, the pathway to methylate and therefore silence the DNA is altered, causing a delay in maturing neurons and synaptogenesis (5). Many functionally different genes are controlled by MECP2 transcription (4). A mutation to the MECP2 gene affects the regulation of the MECP2 protein, but it may

Regulation Of The Internet Essay

5981 words - 24 pages district councils, and still have some of the services (Police and Emergency services) shared between a joint board established with other authorities. Most of the information systems and equipment (IS/IT policy, hardware and software) has been inherited. SSDAM provides flexibility between and within these functions as it suits both large and small projects. It fits each project?s needs because it is scalable and tailor able. It is designed to be