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

- [Narratore] Diverse proteine
regolano negativamente

il ciclo cellulare per impedire
che avvenga la replicazione

prima che le cellule siano pronte.

Durante G!, se il DNA di una
cellula viene danneggiato,

la proteina p53 recluta
enzimi per riparare il DNA

prima che la cellula passi alla fase S.

La p53 stimola anche la
produzione dell'inibitore CVK p21,

che si lega ai complessi CDK-ciclina,

inibendone l'attività e
arrestando il ciclo cellulare.

Se il danno al DNA è troppo da superare,

la p53 può provocare
l'apoptosi, la morte cellulare,

per prevenire la duplicazione
del DNA danneggiato.

Un'altra proteina, proteina
retinoblastoma o Rb,

può tardare il ciclo cellulare
legandosi a fattori di

trascrizione come E2F per
bloccare la trascrizione dei geni

necessari per la transizione da G1 a S.

Quando la cellula è a una taglia
sufficiente alla divisione,

Rb è fosforilato e diventa inattivo,

rilascia E2F, e questi geni
possono ora essere trascritti

e tradotti in enzimi
richiesti per la fase S.

Beckerman, Rachel e Carol Prives. "Regolazione trascrizionale di P53." Cold Spring Harbor Perspectives in Biology 2, n. 8 (1 agosto 2010): a000935. [<a href="https://doi.org/10.1101/cshperspect.a000935" target="__blank">Sorgente</a>]

molecole regolatrici negative

I regolatori positivi consentono a una cellula di avanzare attraverso i checkpoint del ciclo cellulare. I regolatori negativi hanno un ruolo altrettanto importante in quanto terminano la progressione di una cellula attraverso il ciclo cellulare, o la mettono in pausa, fino a quando la cella non soddisfa criteri specifici.

Tre dei regolatori negativi più compresi sono p53, p21 e la proteina retinoblastoma (Rb). I ruoli normativi di ciascuna di queste proteine sono stati scoperti dopo che sono state trovate copie difettose nelle cellule con replica zione incontrollata (cioè il cancro). Queste proteine esercitano la maggior parte dei loro effetti regolatori al checkpoint G1 all'inizio del ciclo cellulare.

P53 influenza fortemente l'impegno di una cellula a dividersi. Risponde al danno del DNA interrompendo il ciclo cellulare ed evocando enzimi per riparare il danno. Se il danno al DNA è irreparabile, p53 può impedire alla cellula di passare attraverso il ciclo cellulare inducendo apoptosi, o morte cellulare.

Un aumento di p53 innesca la produzione di p21. P21 impedisce alla cellula di passare dalla fase G1 alla fase S del ciclo cellulare legandosi ai complessi CDK/cicloni, inibendo le loro azioni regolatorie positive.

Rb regola negativamente il ciclo cellulare agendo su diversi regolatori positivi, principalmente in risposta alle dimensioni delle cellule. L'Rb attivo (defosforilato) si lega ai fattori di trascrizione, impedendo loro di inizializzare la trascrizione genica e, di conseguenza, la produzione di proteine.

Quando Rb è legato al fattore di trascrizione E2F, inibisce la sintesi delle proteine necessarie per la transizione dalla fase G1 alla fase S. Man mano che la cellula diventa più grande, Rb viene gradualmente fosforilata fino a quando non viene inattivata e si stacca da E2F. L'E2F può quindi attivare i geni che producono le proteine necessarie per passare alla fase successiva del ciclo cellulare.

Molecole regolatrici negative

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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Didattica

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Biologia

Cellular Processes

Processi cellulari

Cell Cycle and Division

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KEY TERMS AND CONCEPTS

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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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negative regulator molecules

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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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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Next Generation Science Standards

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Life Science

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Cell Cycle Stop Signals: p53, p21, and Rb

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