7.11
Fatores Moleculares que Afetam a Divisão Celular
Vários fatores externos e internos influenciam a iniciação e inibição da divisão celular. Por exemplo, a morte de células próximas ou a liberação do h…
A divisão celular, ou a fase mitótica do ciclo celular, é controlada por estímulos químicos externos, como fatores de crescimento e hormônios, e fatores internos, como reguladores do ciclo celular.
O ciclo celular é regulado por uma combinação de proteínas chamadas ciclinas e quinases dependentes de ciclina ou Cdks. As concentrações de diferentes ciclinas flutuam com as diferentes fases do ciclo celular.
À medida que uma célula se aproxima do final da fase G2, o nível de ciclina B aumenta. Em altas concentrações, a ciclina B forma um complexo com Cdk1 chamado fator promotor da fase M ou MPF.
A atividade do MPF é regulada por eventos de fosforilação e desfosforilação que determinam se a célula sofre divisão ou não.
Até o final do G2, a Wee1 quinase fosforila os resíduos de tirosina no MPF e o mantém inativo. Isso impede a entrada no ciclo celular e interrompe a célula na fase G2 / M.
Uma vez que o Cdc25 desfosforila o MPF, uma quinase ativadora de Cdk fosforila uma treonina conservada no MPF e a ativa.
Agora as células sofrem mitose e produzem duas células-filhas.
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Q1: What are cyclins and cyclin-dependent kinases and how do they control cell division?
Cyclins and cyclin-dependent kinases (Cdks) are regulatory proteins that control cell division. While Cdk levels remain constant, cyclin concentrations fluctuate during different cell cycle phases. When cyclins bind to Cdks, they become phosphorylated and activated, driving the cell through specific phases. This dynamic regulation ensures orderly progression through the cell cycle.
Q2: How does the M-phase promoting factor activate to trigger mitosis?
The M-phase promoting factor (MPF) forms when cyclin B binds to Cdk1 as the cell approaches the M phase. Wee1 kinase initially keeps MPF inactive by phosphorylating tyrosine residues. Cdc25 phosphatase then dephosphorylates MPF, and a Cdk-activating kinase phosphorylates a threonine residue, fully activating MPF and triggering mitosis.
Q3: What external factors promote or inhibit cell division?
External factors significantly influence cell division initiation. Growth factors and human growth hormone (hGH) promote cell division, while their absence inhibits it. Cell crowding also suppresses division, and the death of nearby cells can stimulate division. These external chemical stimuli work alongside internal regulators to control when cells divide.
Q4: How do negative regulatory proteins like p53 and p21 halt the cell cycle?
Negative regulators including p53 and p21 halt cell cycle progression. When p53 detects DNA damage, it recruits repair enzymes and triggers apoptosis if damage persists. Elevated p53 levels stimulate p21 synthesis, which binds to Cdk/cyclin complexes and blocks progression to the S phase, preventing damaged cells from dividing.
Q5: When do different cyclin levels peak during the cell cycle?
Cyclin concentrations vary predictably across cell cycle phases. Cyclin D rises in G1 and remains high through most phases. Cyclin E peaks at the G1-S junction, while cyclin A is elevated during S and G2 phases. Cyclin B levels rise as the cell approaches M phase, promoting the transition to mitosis.
Q6: What is the role of the retinoblastoma protein in cell cycle regulation?
The retinoblastoma protein (Rb) functions as a negative regulator that halts the cell cycle. It prevents cells from progressing through critical checkpoints until appropriate conditions are met. By blocking cycle progression, Rb ensures that cells complete each phase properly before advancing, maintaining genomic stability.
Q7: How do phosphorylation and dephosphorylation events control MPF activity?
Phosphorylation and dephosphorylation events precisely regulate MPF activity. Wee1 kinase phosphorylates tyrosine residues on MPF to keep it inactive and prevent G2/M transition. Cdc25 phosphatase reverses this by dephosphorylating MPF, allowing a Cdk-activating kinase to phosphorylate threonine and fully activate MPF for mitosis.