What does overexpression of p53 mean?

A tumour that is characterised by p53 overexpression of more than 50% indicates a poor prognosis.

How does p53 interact with cyclin?

p53 inhibits G1/S transition in cells exposed to DNA-damaging agents by causing accumulation of p21CIP1/WAF1 (6, 15), a protein that binds to and inactivates the cyclin-dependent kinases necessary for initiating DNA synthesis (16).

What is cyclin overexpression?

Overexpression of cyclin E, an activator of cyclin-dependent kinase 2, has been linked to human cancer. In cell culture models, the forced expression of cyclin E leads to aneuploidy and polyploidy, which is consistent with a direct role of cyclin E overexpression in tumorigenesis.

What is p53 and how does it affect the cell cycle?

P53 forms a homotetrameric transcription factor that is reported to directly regulate ~500 target genes, thereby controlling a broad range of cellular processes, including cell cycle arrest, cell senescence, DNA repair, metabolic adaptation and cell death.

What happens when p53 accumulates?

P53 is a key tumor suppressor protein. In response to DNA damage, p53 accumulates to high levels in differentiated cells and activates target genes that initiate cell cycle arrest and apoptosis.

Is p53 a cyclin-dependent kinase inhibitor?

The mechanism by which p53 exerts these effects is not clear, but seems to depend on the ability of p53 protein to act as a transcription factor. One of the important p53 transcriptional target genes is the cyclin-dependent kinase (CDK)1 inhibitor p21WAF1/CIP1 (23–26).

Is p53 a type of cyclin?

p53 function is also connected to the activity of other growth regulatory proteins, like E2F and pRb (1,15,16). An important class of proteins controlling the cell division cycle are the cyclins. They are the regulatory subunits in complexes with cyclin-dependent kinases (cdk).

What is the role of cyclin E?

Functions of Cyclin E Cyclin E/CDK2 regulates multiple cellular processes by phosphorylating numerous downstream proteins. Cyclin E/CDK2 plays a critical role in the G1 phase and in the G1-S phase transition. Cyclin E/CDK2 phosphorylates retinoblastoma protein (Rb) to promote G1 progression.

What happens if cyclin D is overexpressed?

Consistent with this function, overexpression of cyclin D1 results in a more rapid progression from the G1 to S phase transition and in a reduced serum dependency in fibroblast cells (14–16). In addition to its role in cell cycle regulation, cyclin D1 is also intricately involved in the regulation of apoptosis.

What is the role of p53 in regulating the cell cycle?

Cell-cycle arrest and apoptosis are the most prominent outcomes of p53 activation. Many studies showed that p53 cell-cycle and apoptosis functions are important for preventing tumor development. p53 also regulates many cellular processes including metabolism, antioxidant response, and DNA repair.

How p53 halt cell-cycle when DNA damage occurs?

When DNA damage is present before the entry into S phase, p53 halts the cell cycle at the G1 phase in part by transcriptionally inducing the cyclin-dependent kinase inhibitor cdkn1a, also known as p21 (el-Deiry et al. 1993).