What do RB and p53 do?
p53 and RB are at the heart of the two main tumour-suppressor pathways that control cellular responses to potentially oncogenic stimuli. Each pathway consists of several upstream regulators and downstream effectors. For simplicity, only four main components in each pathway are shown.
What pathways is p53 involved 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 the difference between p53 and RB?
RB promotes cell cycle arrest in G1 and regulates entry into S phase by inhibiting the E2Fs. p53 mediates several effects, including causing G1 and G2 arrest and promoting apoptosis. Loss of p53 function also promotes genomic instability.
What does RB protein do?
The Rb protein is a tumor suppressor, which plays a pivotal role in the negative control of the cell cycle and in tumor progression. It has been shown that Rb protein (pRb) is responsible for a major G1 checkpoint, blocking S-phase entry and cell growth.
How does p53 regulate apoptosis?
P53 induces apoptosis in nontransformed cells mostly by direct transcriptional activation of the pro-apoptotic BH3-only proteins PUMA and (to a lesser extent) NOXA. Combined loss of the p53 effectors of apoptosis (PUMA plus NOXA) and cell cycle arrest/cell senescence (p21) does not cause spontaneous tumour development.
In what way can p53 regulate RB?
p53 suppresses the cell proliferation mediated by the Rb-E2F pathway. Phosphorylation of Rb by CDK4/6-cyclin D and CDK2-cyclin E causes the dissociation of Rb from E2F to promote cell cycle progression.
What is pRB gene responsible for?
Normal Function. The RB1 gene provides instructions for making a protein called pRB. This protein acts as a tumor suppressor, which means that it regulates cell growth and keeps cells from dividing too fast or in an uncontrolled way.
How does pRB regulate cell cycle?
One function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide. When the cell is ready to divide, pRb is phosphorylated, inactivating it, and the cell cycle is allowed to progress.
What is pRb gene responsible for?
What is the function of the Rb protein?
How does p53 regulate cell proliferation in response to DNA damage?
After UV-induced DNA damage, activated p53 induces the expression of p48 and XPC, thus increasing the cell’s capacity to locate and target DNA damage for repair. At least two observations support the trans requirement for p53 in regulating NER.
How does p53 regulate cell proliferation?
In the planarians, p53 regulates proliferation and self-renewal in adult stem cell lineages [37]. Similarly in mouse studies, p53 activation through the specific inactivation of Mdm2 in the gut, a highly proliferative tissue, leads to apoptosis and proliferation that compensates for cell loss [38].