Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication.
Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication.
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DOI：
10.1038/ncomms4649
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发表时间：
2014-04-14
影响因子：
16.6
通讯作者：
Pasini, Diego
中科院分区：
文献类型：
--
作者：
Piunti, Andrea;Rossi, Alessandra;Cerutti, Aurora;Albert, Mareike;Jammula, Sriganesh;Scelfo, Andrea;Cedrone, Laura;Fragola, Giulia;Olsson, Linda;Koseki, Haruhiko;Testa, Giuseppe;Casola, Stefano;Helin, Kristian;di Fagagna, Fabrizio d'Adda;Pasini, Diego
PRC1 和 PRC2 促进增殖的能力是将多梳 (PcG) 活性与癌症联系起来的一个主要特征。 PcG 沉默肿瘤抑制基因座 Ink4a/Arf 的表达，其产物正向调节 pRb 和 p53 功能。 PcG 活性增强是人类肿瘤的常见特征，PcG 抑制已被提议作为癌症治疗的策略。然而，人类癌症中 pRb/p53 反应的反复失活引发了一个关于 PcG 蛋白独立于该检查点影响细胞增殖的能力的问题。在这里，我们证明 PRCs 独立于 Ink4a/Arf-pRb-p53 途径调节细胞增殖和转化。我们提供的证据表明 PRCs 定位于复制叉，并且其功能的丧失直接影响 DNA 复制叉的进展和对称性。因此，我们发现了 PcG 的一种新活性，可以独立于主要细胞周期限制检查点来调节细胞增殖。 已知 Polycomb (PcG) 蛋白可通过沉默肿瘤抑制因子 Ink4A-Arf 的表达来促进细胞增殖。皮翁蒂等人。研究表明，PcG 蛋白还独立于其作用调节肿瘤进展，揭示了复制叉进展中对 PRC1 和 PRC2 的需求。
The ability of PRC1 and PRC2 to promote proliferation is a main feature that links polycomb (PcG) activity to cancer. PcGs silence the expression of the tumour suppressor locus Ink4a/Arf, whose products positively regulate pRb and p53 functions. Enhanced PcG activity is a frequent feature of human tumours, and PcG inhibition has been proposed as a strategy for cancer treatment. However, the recurrent inactivation of pRb/p53 responses in human cancers raises a question regarding the ability of PcG proteins to affect cellular proliferation independently from this checkpoint. Here we demonstrate that PRCs regulate cellular proliferation and transformation independently of the Ink4a/Arf-pRb-p53 pathway. We provide evidence that PRCs localize at replication forks, and that loss of their function directly affects the progression and symmetry of DNA replication forks. Thus, we have identified a novel activity by which PcGs can regulate cell proliferation independently of major cell cycle restriction checkpoints. Polycomb (PcG) proteins are known to promote cell proliferation by silencing expression of the tumour suppressor Ink4A-Arf. Piunti et al. show that PcG proteins also regulate tumour progression independently of this role, revealing a requirement for PRC1 and PRC2 in replication fork progression.
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影响因子：
64.8
作者：
Di Micco, Raffaella;Fumagalli, Marzia;di Fagagna, Fabrizio d'Adda
通讯作者：
di Fagagna, Fabrizio d'Adda
影响因子：
21.3
作者：
Campaner, Stefano;Doni, Mirko;Amati, Bruno
通讯作者：
Amati, Bruno
影响因子：
16
作者：
Cao, R;Zhang, Y
通讯作者：
Zhang, Y
影响因子：
11.2
作者：
Datta, Sonal;Hoenerhoff, Mark J.;Dimri, Goberdhan P.
通讯作者：
Dimri, Goberdhan P.
影响因子：
4.8
作者：
Bianco, Julien N.;Poli, Jerome;Pasero, Philippe
通讯作者：
Pasero, Philippe