What is the main function of p53?
Normal Function 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.
Does p53 act as a monomer?
These data led Sakaguchi et al. (1997) to suggest that because the cellular concentration of p53 is very low in human cells with undamaged DNA (1 to 10 nM), p53 may exist in these cells predominantly as monomers.
Why is p53 a tetramer?
The p53 tumor suppressor protein is a tetramer that binds sequence-specifically to a DNA consensus sequence consisting of two consecutive half-sites, with each half-site being formed by two head-to-head quarter-sites (–><– –><–).
Does p53 function as a homodimer?
We show that p53 binds to a target oligonucleotide as a protein homodimer and that p53 dimerisation is required for detectable DNA binding. Thus, both transcription transactivation and tumour suppressor functions act independently of p53 protein self-association and DNA binding.
What role does p53 play in apoptosis?
The p53 tumor suppressor acts to integrate multiple stress signals into a series of diverse antiproliferative responses. One of the most important p53 functions is its ability to activate apoptosis, and disruption of this process can promote tumor progression and chemoresistance.
Why is it important to study p53?
Oncogenic activation of RAS, p53 protein overexpression, and p53 gene mutations have been reported as prognostic markers of poor outcome in NSCLC patients. Because p53 is an important factor in the regulation and initiation of DNA repair, aberrations in p53 expression may also affect response to chemotherapy.
How many domains does p53 have?
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 a tetramer in biology?
A tetramer (/ˈtɛtrəmər/) (tetra-, “four” + -mer, “parts”) is an oligomer formed from four monomers or subunits. The different sub-units may have each their own activity, such as binding biotin in avidin tetramers, or have a common biological property, such as the allosteric binding of oxygen in hemoglobin.
How does p53 bind the DNA?
p53 activates or inhibits transcription by binding to specific DNA target sequences. The p53 binding site consists of two half-sites 5´-PuPuPuC(A/T)(T/A)GPyPyPy-3´, linked by a 0-13 nucleotide spacer.
What is a Tetramerization domain?
K+ channel tetramerisation domain is the N-terminal, cytoplasmic tetramerisation domain (T1) of voltage-gated K+ channels. It defines molecular determinants for subfamily-specific assembly of alpha-subunits into functional tetrameric channels.