Name: cell cycle stop signals: p53, p21, and rb
Uploaded: 2019-03-11T09:21:14.000Z
Duration: 1 min 23 s
Channel: JoVE

K12 Standards

Virginia  Standards of Learning

HIgh School

Biology

BIO.3

BIO.3.c

Negative Regulator Molecules

Several proteins negatively regulate the cell cycle to prevent replication from occurring before cells are ready.

During G1 if a cell&#39;s DNA is damaged, the protein P53 recruits enzymes to repair the DNA before the cell transitions to S-phase.

P53 also stimulates the production of the CDK inhibitor, P21, which binds to CDK cyclin complexes inhibiting their activity and arresting the cell cycle.

If DNA damage is too much to overcome, P53 can prompt apoptosis, cell death, to prevent duplication of damaged DNA.

Another protein, retinoblastoma protein or Rb, can slow the cell cycle by binding to transcription factors such as E2F to block the transcription of genes necessary for the G1 to S transition.

Once the cell grows to a sufficient size for division, Rb is phosphorylated and becomes inactive, releases E2F, and these genes can now be transcribed and translated into enzymes required for S-phase.

negative regulator molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell&rsquo;s progression through the cell cycle&mdash;or pause it&mdash;until the cell meets specific criteria.

Three of the best-understood negative regulators are p53, p21, and retinoblastoma protein (Rb). The regulatory roles of each of these proteins were discovered after faulty copies were found in cells with uncontrolled replication (i.e., cancer). These proteins exert most of their regulatory effects at the G1 checkpoint early in the cell cycle.

P53 strongly influences a cell&rsquo;s commitment to divide. It responds to DNA damage by discontinuing the cell cycle and summoning enzymes to repair the damage. If the DNA damage is irreparable, p53 can prevent the cell from proceeding through the cell cycle by inducing apoptosis, or cell death.

An increase in p53 triggers the production of p21. P21 prevents the cell from transitioning from the G1 to the S phase of the cell cycle by binding to CDK/cyclin complexes, inhibiting their positive regulatory actions.

Rb negatively regulates the cell cycle by acting on different positive regulators, mainly in response to cell size. Active (dephosphorylated) Rb binds to transcription factors, preventing them from initiating gene transcription and, hence, protein production.

When Rb is bound to the transcription factor E2F, it inhibits the synthesis of proteins needed to transition from the G1 to the S phase. As the cell becomes larger, Rb is gradually phosphorylated until it is inactivated and detaches from E2F. E2F can then activate genes that produce the proteins needed to proceed to the next cell cycle stage.

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a ...

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Cellular Processes

Cell Cycle and Division

KEY TERMS AND CONCEPTS

cell cycle stop signals: p53, p21, and rb

Cell cycle stop signals help control when a cell can move forward through division. Negative regulators pause or end the cell cycle until the cell meets the right conditions. Three well-studied negative regulators are p53, p21, and retinoblastoma protein, or Rb. Their roles became clear after faulty versions were found in cancer cells that kept replicating uncontrollably.

These proteins act mostly at the G1 checkpoint, which comes early in the cell cycle. P53 has a strong effect on whether a cell commits to divide. When DNA is damaged, p53 stops the cell cycle and calls in enzymes that repair the damage. If the damage cannot be fixed, p53 can trigger apoptosis, which is programmed cell death.

P53 also increases the production of p21. P21 blocks the shift from G1 to S phase by binding to CDK/cyclin complexes. CDKs are cyclin-dependent kinases, and these complexes normally help push the cell forward. By blocking them, p21 prevents their positive regulatory action.

Rb controls the cell cycle in a different way, especially in response to cell size. When Rb is active, or dephosphorylated, it binds to transcription factors and keeps them from starting gene transcription. This lowers protein production. When Rb binds the transcription factor E2F, it prevents the proteins needed to move from G1 to S phase from being made.

As the cell grows larger, Rb becomes gradually phosphorylated and is inactivated. It then detaches from E2F. E2F can then turn on genes that make the proteins needed for the next cell cycle stage. In this way, Rb helps make sure the cell only advances when it has grown enough.

Cell Cycle Stop Signals: p53, p21, and Rb

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Cell cycle stop signals help control when a cell can move forward through division. Negative regulators pause or end the cell cycle until the cell meets the right conditions. Three well-studied negative regulators are p53, p21, and retinoblastoma protein, or Rb. Their roles became clear after faulty versions were found in cancer cells that kept replicating uncontrollably. These proteins act mostly at the G1 checkpoint, which comes early in the cell cycle. P53 has a strong effect on whether a...

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key terms and concepts

Learn how p53, p21, and Rb act as cell cycle stop signals at the G1 checkpoint, repairing DNA damage or pausing division until a cell is ready.

Cell Cycle Stop Signals: p53, p21, and Rb | JoVE K12

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Cell Cycle Stop Signals: p53, p21, and Rb

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