What are the domains of p53?
The p53 family proteins share significant similarity at the amino-acid level within three domains: the transcriptional activation domain (AD), the sequence-specific DNA-binding domain (DBD), and the tetramerization domain (TD) (Figure 1a).
What is the function of the protein p53?
A gene that makes a protein that is found inside the nucleus of cells and plays a key role in controlling cell division and cell death. Mutations (changes) in the p53 gene may cause cancer cells to grow and spread in the body.
What are two of the roles of the p53 protein?
p53 is a tumor suppressor protein and transcription factor that regulates cell division and prevents tumor formation by stopping cells with mutated or damaged DNA from dividing and signaling for them to undergo apoptosis through transcriptional regulation.
What protein does p53 produce?
The p53 gene has been mapped to chromosome 17. In the cell, p53 protein binds DNA, which in turn stimulates another gene to produce a protein called p21 that interacts with a cell division-stimulating protein (cdk2).
Why is the complexing domain of p53 so important to its function?
Why is the complexing domain of p53 so important to its function (slide 5)? A single p53 molecule isn’t fully functional since it has to form a complex before it can bind to DNA and activate other genes.
Which domain of p53 is bound by MDM2?
transactivation domain
The MDM2 protein, in turn, can bind the transactivation domain of p53, inhibiting further p53 activity as a transcription factor (6, 11, 12).
Is p53 a hub protein?
The tumor suppressor p53 is a central hub in a molecular network controlling cell proliferation and death in response to potentially oncogenic conditions, and a wide array of covalent modifications and protein interactions modulate the nuclear and cytoplasmic activities of p53.
Why p53 is considered the guardian of the genome?
By stopping cells with mutated or damaged DNA from dividing, p53 helps prevent the development of tumors. Because p53 is essential for regulating DNA repair and cell division, it has been nicknamed the “guardian of the genome.”
What are the structural and oligomerization domains of p53?
To identify structural and oligomerization domains in p53, we have investigated the physical properties of purified segments of p53. The central, specific DNA-binding domain within murine amino acids 80 to 320 and human amino acids 83 to 323 behaves predominantly as monomers during analysis by sedimentation, gel filtration, and gel electrophoresis.
Do murine p53 and human p53 form tetramers?
Amino acids 330 to 390 of murine p53 and amino acids 340 to 393 of human p53, which have been implicated by Sturzbecher et al. in tetramerization (H.-W. Sturzbecher, R. Brain, C. Addison, K. Rudge, M. Remm, M. Grimaldi, E. Keenan, and J. R. Jenkins, Oncogene 7:1513-1523, 1992), do not form stable tetramers under our conditions.
What is the C terminus of p53 made of?
Like wild-type p53, the C terminus, consisting of murine amino acids 280 to 390 and human amino acids 283 to 393, behaves anomalously during gel filtration and apparently has a nonglobular shape. Within this region, murine amino acids 315 to 350 and human amino acids 323 to 355 are sufficient for assembly of stable tetramers.
Is the central region of p53 globular in shape?
The central, specific DNA-binding domain within murine amino acids 80 to 320 and human amino acids 83 to 323 behaves predominantly as monomers during analysis by sedimentation, gel filtration, and gel electrophoresis. This consistent behavior argues that the central region of p53 is globular in shape.