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

Kilka białek negatywnie reguluje cykl komórkowy, aby zapobiec replikacji, zanim komórki będą gotowe.

Podczas G1, jeśli DNA komórki jest uszkodzone, białko P53 rekrutuje enzymy do naprawy DNA, zanim komórka przejdzie do fazy S.

P53 stymuluje również produkcję inhibitora CDK, P21, który wiąże się z kompleksami cykliny CDK, hamując ich aktywność i zatrzymując cykl komórkowy.

Jeśli uszkodzenie DNA jest zbyt duże do pokonania, P53 może wywołać apoptozę, śmierć komórki, aby zapobiec duplikacji uszkodzonego DNA.

Inne białko, białko siatkówczaka lub Rb, może spowolnić cykl komórkowy poprzez wiązanie się z czynnikami transkrypcyjnymi, takimi jak E2F, w celu zablokowania transkrypcji genów niezbędnych do przejścia G1 do S.

Gdy komórka urośnie do rozmiaru wystarczającego do podziału, Rb ulega fosforylacji i staje się nieaktywny, uwalnia E2F, a geny te mogą być teraz transkrybowane i translowane na enzymy wymagane w fazie S.

Beckerman, Rachel i Carol Prives. "Regulacja transkrypcji przez P53". Cold Spring Harbor Perspectives in Biology 2, nr 8 (1 sierpnia 2010): a000935. [<a href="https://doi.org/10.1101/cshperspect.a000935" target="__blank">Źródło</a>]

negatywne cząsteczki regulacyjne

Pozytywne regulatory umożliwiają komórce przejście przez punkty kontrolne cyklu komórkowego. Ujemne regulatory odgrywają równie ważną rolę, ponieważ przerywają przejście komórki przez cykl komórkowy — lub wstrzymują go — do czasu, aż komórka spełni określone kryteria.

Trzy z najlepiej poznanych negatywnych regulatorów to p53, p21 i białko siatkówczaka (Rb). Rolę regulacyjną każdego z tych białek odkryto po znalezieniu wadliwych kopii w komórkach z niekontrolowaną replikacją (tj. nowotworem). Białka te wywierają większość swoich efektów regulacyjnych w punkcie kontrolnym G1 na początku cyklu komórkowego.

P53 silnie wpływa na zaangażowanie komórki w podział. Reaguje na uszkodzenia DNA, przerywając cykl komórkowy i przywołując enzymy w celu naprawy uszkodzeń. Jeśli uszkodzenie DNA jest nieodwracalne, p53 może uniemożliwić komórce przejście przez cykl komórkowy poprzez indukcję apoptozy, czyli śmierci komórki.

Wzrost p53 wyzwala produkcję p21. P21 zapobiega przejściu komórki z fazy G1 do fazy S cyklu komórkowego poprzez wiązanie się z kompleksami CDK/cyklina, hamując ich pozytywne działanie regulacyjne.

Rb negatywnie reguluje cykl komórkowy, działając na różne pozytywne regulatory, głównie w odpowiedzi na wielkość komórki. Aktywny (defosforylowany) Rb wiąże się z czynnikami transkrypcyjnymi, uniemożliwiając im inicjację transkrypcji genów, a tym samym produkcję białka.

Gdy Rb wiąże się z czynnikiem transkrypcyjnym E2F, hamuje syntezę białek potrzebnych do przejścia z fazy G1 do fazy S. W miarę jak komórka staje się większa, Rb ulega stopniowej fosforylacji, aż do inaktywacji i odłączenia się od E2F. E2F może następnie aktywować geny wytwarzające białka potrzebne do przejścia do następnego etapu cyklu komórkowego.

Negatywne cząsteczki regulacyjne

Regulatory dodatnie pozwalają komórce przejść przez punkty kontrolne cyklu komórkowego. Negatywne organy regulacyjne odgrywają równie ważną rolę, ponieważ kończą ...

Education

JoVE Core

Biologia

Cellular Processes

Procesy komórkowe

Cell Cycle and Division

Cykl komórkowy i podziały komórkowe

KEY TERMS AND CONCEPTS

Kluczowe terminy i pojęcia

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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positive regulator molecules

Cyclins and CDKs in the Cell Cycle

Cyclins and CDKs help control the cell cycle, the process that produces daughter cells. Cells use internal checkpoints to make sure their size, energy reserves, and DNA are ready before they move forward. At these checkpoints, positive regulators help the cell continue, while negative regulators slow or stop it. The main positive regulators are cyclins and cyclin-dependent kinases, or CDKs. These proteins are found in eukaryotes, from yeast to humans. Cyclins are grouped by the stage they help...

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...

cancer

Cancer Treatment, Personalization, and Cell Growth

Cancer develops when mutations affect genes that control cell division. Those changes can remove the normal brakes on growth and lead to uncontrolled cell proliferation. Modern science and medicine have improved how cancer is understood and treated, and some patients can now be cured. There is still no single cure for cancer because cancer is not one disease. It is a large group of many diseases. Even when two people have the same mutation in an oncogene or a tumor suppressor gene, their...

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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