What is the structure of p53 protein?

Domain structure of p53. p53 contains a natively unfolded amino-terminal transactivation domain (TAD), which can be further subdivided into the subdomains TAD1 and TAD2, followed by a proline-rich region (PRR). The structured DNA-binding and tetramerization domains (OD) are connected through a flexible linker region.

Does p53 have ubiquitination?

An important control mechanism for p53 regulation is through ubiquitination. It has been shown that p53 ubiquitination is highly dynamic and reversible, with monoubiquitination and polyubiquitation playing important and distinct roles in the functions of p53.

What pathway is p53 in?

In addition to the intrinsic pathway, p53 regulates a series of genes that initiate the extrinsic apoptotic pathway (Fas ligand, killer Dr receptor), resulting in the caspase-8 and -3 activities and apoptosis.

What is ubiquitination proteasome pathway?

The ubiquitin-proteasome pathway (UPP) is one of the major destruction ways to control the activities of different proteins. The function of UPP is to eliminate dysfunctional/misfolded proteins via the proteasome, and these specific functions enable the UPP to regulate protein quality in cells.

How does p53 bind the DNA?

p53 tumor suppressor binds to DNA using all four of its arms. The typical binding site for the whole molecule is composed of three parts: a specific binding site for two p53 domains, a variable stretch of 0 to 13 base pairs, and a second specific binding site for the other two p53 domains.

How does the p53 protein work?

This protein acts as a tumor suppressor, which means that it regulates cell division by keeping cells from growing and dividing (proliferating) too fast or in an uncontrolled way. The p53 protein is located in the nucleus of cells throughout the body, where it attaches (binds) directly to DNA.

Is Mdm2 a ubiquitin?

Mdm2 is ubiquitinated and is degraded by the proteasome. The proteasome consequently contributes to the maintenance of the balance between levels of p53 and Mdm2.

How does p53 function as a tumor suppressor protein?

The TP53 gene provides instructions for making a protein called tumor protein p53 (or p53). This protein acts as a tumor suppressor, which means that it regulates cell division by keeping cells from growing and dividing (proliferating) too fast or in an uncontrolled way.

Where does ubiquitin proteasome pathway occur?

The rapid degradation of ubiquitinated proteins is catalyzed by the 26S proteasome. This structure is found in the nucleus and the cytosol of all cells and constitutes approximately 1 to 2% of cell mass (39).

How does ubiquitination play a role in proteasome function?

The ubiquitin–proteasome system (UPS) controls almost all basic cellular processes—such as progression through the cell cycle, signal transduction, cell death, immune responses, metabolism, protein quality control and development—by degrading short-lived regulatory or structurally aberrant proteins.