Can Rb induce apoptosis?
In our earlier experiments, induction of wild-type pRB and RB_SP consistently yielded a small but significant increase in apoptosis even in the absence of TNFα treatment.
How does pRb regulate the cell cycle?
Abstract. pRB, the tumor suppressor product of the retinoblastoma susceptibility gene, is regarded as one of the key regulators of the cell cycle. This protein exerts its growth suppressive effect through its ability to bind and interact with a variety of cellular proteins.
How does Rb halt the cell cycle?
The binding of RB to E2F proteins either blocks the recruitment of transcriptional co-activators or recruits transcriptional co-repressors to these promoters, thus repressing the expression of these genes and halting the G1/S cell cycle transition.
During which phase would a cell commit apoptosis?
Hematopoietic cells can undergo apoptosis at all stages of cell cycle as noted by Bertrand. However, mesenchymal or epithelial cells usually undergo apoptosis at the G1/S or G2/M phase of the cell cycle.
What is the role of pRB?
pRB is one member of a family of structurally and functionally conserved proteins that play a key role in negative regulation of the cell cycle via binding to E2F transcription factors. Despite such similarity, pRB is the only member required for DNA damage-induced arrest.
What is pRB function?
The retinoblastoma protein (protein name abbreviated pRb; gene name abbreviated Rb, RB or RB1) is a tumor suppressor protein that is dysfunctional in several major cancers. One function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide.
How does pRB function to keep cells at the G1 checkpoint?
With the activation of CDK4, CDK6 and CDK2-E in the G1 phase, the pRB-E2F complex is released and the cell cycle progresses through the S phase. The pRB is again activated by phosphatases, that allow the hypophosphorylation of the protein and stop the cell cycle in G0/G1.
What is the consequence of Rb hyperphosphorylation?
Hyperphosphorylated Rb in this context inhibits the apoptotic activity of pp32 and stimulates proliferation through yet undefined mechanisms. This study further supports the notion that Rb phosphorylation status is important for the regulation of apoptosis by Rb.
What triggers apoptosis?
Apoptosis can be triggered by mild cellular injury and by various factors internal or external to the cell; the damaged cells are then disposed of in an orderly fashion. As a morphologically distinct form of programmed cell death, apoptosis is different from the other major process of cell death known as necrosis.
What are the four main stages of apoptosis?
To illustrate these apoptosis events and how to detect them, Bio-Rad has created a pathway which divides apoptosis into four stages: induction, early phase, mid phase and late phase (Figure 1).
How does pRb function to keep cells at the G1 checkpoint?
The pRb protein represses gene transcription, required for transition from G1 to S phase, by directly binding to the transactivation domain of E2F and by binding to the promoter of these genes as a complex with E2F.
How does the Rb tumor suppressor function quizlet?
Brake #1: The Rb protein binds up an important gene regulatory protein called E2F. When phosphorylated, Rb lets go of E2F, which turns on transcription of many things including G1/S cyclins. Rb is a tumor suppressor. Rb = retinoblastoma = cancer of the eye.
What is the role of pRB in apoptosis?
Additional support for a protective role of pRb against apoptosis comes from the observation that pRb is the target of caspases. pRb is cleaved in different apoptotic systems such as tumor necrosis factor-, staurosporine-, Fas- and cytosine arabinoside-induced apoptosis [41–43].
Is there a link between the cell cycle and apoptosis?
An argument in favor of a link between the cell cycle and apoptosis arises from the accumulated evidence that manipulation of the cell cycle may either prevent or induce an apoptotic response.
Is PRB an anti-apoptotic factor?
pRb is not only a growth suppressor but also an anti-apoptotic factor. In vivostudies show that pRb knockout mice die in uteroat 14 to 15 days [37]. They have defects in the haematopoietic system and have impaired development of the central and the peripheral nervous system because of massive cell death.
How does p53 cause cell cycle arrest?
In damaged cells, p53 is activated and causes cell cycle arrest by inducing p21 and by inhibiting pRb phosphorylation by Cdks. If pRb is mutated, the cell cycle is not arrested and the conflict between the p53 signal to stop cell growth and the Cdk signal to proliferate leads to apoptosis.