35.13
特定蛋白的逐步破坏对于细胞周期的进展和完成是必要的。 这些蛋白被泛素连接酶泛素化,然后被蛋白酶体降解。 SCF (Skp1/Cullin/F-box) 和后期促进复合物 (APC) 是参与细胞周期进程的两种重要的泛素连接酶。 SCF 在整个细胞周期中都处于活跃状态,而 APC 在中期到后期的转变过程…
有丝分裂后期的成功完成还依赖于一种称为后期促进复合物或周期素体(APC/C)的泛素连接酶的活性。
在向后期过渡的过程中,Cdc20 蛋白结合并激活 APC/C。被激活的 APC/C 对调控蛋白 S 型周期蛋白和 M 型周期蛋白进行泛素化,从而使其靶向蛋白酶体降解。
细胞周期蛋白的降解会抑制大多数周期蛋白依赖性激酶(Cdks)的活性。周期蛋白依赖性激酶活性的缺失使得磷酸酶能够去磷酸化细胞内大多数Cdk底物,这是完成后期(anaphase)所必需的。
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Q1: What is the anaphase promoting complex and what does it do in the cell cycle?
The anaphase promoting complex (APC) is a regulatory protein complex that controls cell cycle progression by targeting proteins for degradation. It acts as a ubiquitin ligase, marking specific proteins with ubiquitin tags that signal their destruction. This degradation is essential for allowing cells to transition through different phases of mitosis and cytokinesis.
Q2: How does the anaphase promoting complex regulate chromatid separation?
The APC controls chromatid separation by degrading proteins that hold sister chromatids together. When APC targets cohesin and securin for destruction, sister chromatids can separate and move to opposite poles of the cell. This degradation is critical for ensuring proper chromosome distribution during anaphase.
Q3: Why is the anaphase promoting complex considered a ubiquitin ligase?
The APC functions as a ubiquitin ligase because it catalyzes the attachment of ubiquitin proteins to target substrates. This ubiquitination marks proteins for degradation by the proteasome. The APC's role as a ubiquitin ligase makes it a key regulatory mechanism for controlling protein levels during cell division.
Q4: What proteins does the anaphase promoting complex target for degradation?
The APC targets multiple proteins essential for maintaining cell cycle checkpoints, including securin and cyclins. Securin degradation allows cohesin cleavage and chromatid separation. Cyclin degradation reduces kinase activity, allowing cells to exit mitosis and progress through the cell cycle phases.
Q5: How does the anaphase promoting complex ensure proper cell cycle regulation?
The APC ensures proper cell cycle regulation by responding to checkpoint signals and degrading proteins at specific times. Its activity is tightly controlled by regulatory proteins and checkpoint mechanisms that prevent premature progression. This temporal regulation guarantees that cells complete one phase before entering the next.
Q6: What happens if the anaphase promoting complex malfunctions during cell division?
If the APC malfunctions, cells may fail to degrade critical regulatory proteins, causing improper chromosome segregation and aneuploidy. Defective APC function can lead to uncontrolled cell division and genomic instability. This dysfunction is associated with cancer development and other cellular disorders.