How does p53 induce 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.
How activation of p53 can signal the intrinsic pathway of apoptosis?
Thus, in response to DNA damage, p53 activates the intrinsic mitochondrial apoptotic pathway by inducing the expression of at least three Bcl2 pro-apoptotic family members, shifting the balance towards pro-apoptotic effects.
How does the p53 pathway work?
The p53 pathway is composed of a network of genes and their products that are targeted to respond to a variety of intrinsic and extrinsic stress signals that impact upon cellular homeostatic mechanisms that monitor DNA replication, chromosome segregation and cell division (Vogelstein et al., 2000).
What can induce apoptosis?
In cell lines intrinsic apoptosis can be induced by stimuli including removing growth factor supplements from cell media, exposure to UV light or by exerting other stressful conditions on the cell as shown on the left of Figure 1.
Does p53 cause intrinsic or extrinsic apoptosis?
All these facts come to stress the important role of p53 protein in intrinsic apoptotic pathway. The p53 protein also activates the “death” receptors (belonging to the TNF-R family) and directly caspase 8 – both components of extrinsic apoptotic pathway.
What is intrinsic pathway of apoptosis?
The intrinsic apoptosis pathway is initiated by, for example, chemotherapy and/or radiotherapy. It is activated by a range of exogenous and endogenous stimuli, such as DNA damage, ischemia, and oxidative stress. Moreover, it plays an important function in development and in the elimination of damaged cells.
Is Ras a tumor suppressor gene?
The Ras Effector RASSF2 Is a Novel Tumor-Suppressor Gene in Human Colorectal Cancer.