細(xì)胞周期檢查點(diǎn)的快速反應(yīng)機(jī)制
7月7號(hào)報(bào)道發(fā)現(xiàn)G1期的檢查點(diǎn)是一個(gè)復(fù)雜的過程。在此周期的cell cycle對(duì)DNA損傷有兩步反應(yīng),首先是G1期的快速停止,此過程不需p53,然后是依賴于p53的對(duì)cell cycel停止的維持。
原來一直認(rèn)為當(dāng)細(xì)胞受到損傷如離子射線時(shí),首先是p53被ATM激酶磷酸化,再促進(jìn)多個(gè)基因轉(zhuǎn)錄激活,如p21cip1,p21抑制cyclin E/CDK2復(fù)合物,進(jìn)行G1期的抑制,但此過程通常要8個(gè)小時(shí)才能發(fā)生,而離子射線誘導(dǎo)的G1期停止幾乎是立即完成的。
為了解開這個(gè)謎團(tuán),Agami,R etal. 構(gòu)建了一個(gè)p53失活的細(xì)胞系,進(jìn)行離子輻射刺激后,發(fā)現(xiàn)cyclinD1下調(diào),這種下調(diào)是由于cyclinD1本身的RXXL(destructure-box-like
motif)引起的。在受到刺激后,cyclinD1被APC降解,釋放出p21,p21即對(duì)cyclinE/CDK2復(fù)合物產(chǎn)生抑制,完成了早期快速抑制的過程,而p53介導(dǎo)的p21上升看來是起后期維持作用的。這個(gè)問題得到了解決,但在檢測(cè)DNA損傷的反應(yīng)中,可能還有許多不為人知的故事。
相關(guān)文章:
Original research paper
Agami, R. & Bernards, R.
Distinct initiation and maintenance mechanisms cooperate to induce G1 Cell cycle arrest in response to DNA damage. Cell 102, 55–66 (2000). REVIEWS
Donjerkovic, D. & Scott,D. W. Regulation of the G1 phase of the mammalian cell cycle. Cell
Res. 10, 1–16 (2000).
Fang, G., Yu, H. &
Kirschner, M. W. Control of mitotic transitions by the
anaphase-promoting complex. Phil. Trans R. Soc. Lond. B 354,1583–1390 (1999).
Further reading MAiland, N. et al. Rapid
destruction of human Cdc25A in response to DNA damage. Science 288,1425–1429 (2000).
新思路
新技術(shù)—其他文章, 百拇醫(yī)藥
原來一直認(rèn)為當(dāng)細(xì)胞受到損傷如離子射線時(shí),首先是p53被ATM激酶磷酸化,再促進(jìn)多個(gè)基因轉(zhuǎn)錄激活,如p21cip1,p21抑制cyclin E/CDK2復(fù)合物,進(jìn)行G1期的抑制,但此過程通常要8個(gè)小時(shí)才能發(fā)生,而離子射線誘導(dǎo)的G1期停止幾乎是立即完成的。
為了解開這個(gè)謎團(tuán),Agami,R etal. 構(gòu)建了一個(gè)p53失活的細(xì)胞系,進(jìn)行離子輻射刺激后,發(fā)現(xiàn)cyclinD1下調(diào),這種下調(diào)是由于cyclinD1本身的RXXL(destructure-box-like
motif)引起的。在受到刺激后,cyclinD1被APC降解,釋放出p21,p21即對(duì)cyclinE/CDK2復(fù)合物產(chǎn)生抑制,完成了早期快速抑制的過程,而p53介導(dǎo)的p21上升看來是起后期維持作用的。這個(gè)問題得到了解決,但在檢測(cè)DNA損傷的反應(yīng)中,可能還有許多不為人知的故事。
相關(guān)文章:
Original research paper
Agami, R. & Bernards, R.
Distinct initiation and maintenance mechanisms cooperate to induce G1 Cell cycle arrest in response to DNA damage. Cell 102, 55–66 (2000). REVIEWS
Donjerkovic, D. & Scott,D. W. Regulation of the G1 phase of the mammalian cell cycle. Cell
Res. 10, 1–16 (2000).
Fang, G., Yu, H. &
Kirschner, M. W. Control of mitotic transitions by the
anaphase-promoting complex. Phil. Trans R. Soc. Lond. B 354,1583–1390 (1999).
Further reading MAiland, N. et al. Rapid
destruction of human Cdc25A in response to DNA damage. Science 288,1425–1429 (2000).
新思路
新技術(shù)—其他文章, 百拇醫(yī)藥
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