RBF1 promotes chromatin condensation through a conserved interaction with the Condensin II protein dCAP-D3
RBF1 promotes chromatin condensation through a conserved interaction with the Condensin II protein dCAP-D3
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DOI：
10.1101/gad.1631508
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发表时间：
2008-04-15
影响因子：
10.5
通讯作者：
Dyson, Nicholas J.
中科院分区：
文献类型：
--
作者：
Longworth, Michelle S.;Herr, Anabel;Dyson, Nicholas J.
果蝇视网膜母细胞瘤蛋白家族（RBF 1和RBF 2）及其哺乳动物同源物（pRB、p130和p107）最为人所知的是通过抑制E2 F依赖性转录来调节G1/S转换。然而，RB家族成员还具有额外的功能。在这里，我们报告rbf 1突变幼虫有广泛的缺陷，在有丝分裂过程中染色质凝聚。我们描述了RBF 1和dCAP-D3之间的一种新的相互作用，dCAP-D3是将RBF 1与染色体结构调节联系起来的Condensin II复合物的非SMC组分。RBF 1与dCAP-D3物理相互作用，RBF 1和dCAP-D3部分共定位在多线染色体上，并且RBF 1是dCAP-D3与染色质有效缔合所必需的。dCap-D3突变体也表现出染色质凝聚缺陷，并且dCap-D3的突变等位基因抑制由RBF 1过表达诱导的细胞和发育表型。有趣的是，这种相互作用在苍蝇和人类之间是保守的。pRB在pRB缺陷型人肿瘤细胞系中的再表达以依赖于pRB的LXCXE结合裂缝的方式促进hCAP-D3的染色质缔合。这些结果揭示了pRB/RBF 1和染色质凝聚之间的意外联系，提供了一种机制，通过这种机制，RB家族成员在人类肿瘤细胞中的功能失活可能导致基因组不稳定性。
The Drosophila retinoblastoma family of proteins (RBF1 and RBF2) and their mammalian homologs (pRB, p130, and p107) are best known for their regulation of the G1/S transition via the repression of E2F-dependent transcription. However, RB family members also possess additional functions. Here, we report that rbf1 mutant larvae have extensive defects in chromatin condensation during mitosis. We describe a novel interaction between RBF1 and dCAP-D3, a non-SMC component of the Condensin II complex that links RBF1 to the regulation of chromosome structure. RBF1 physically interacts with dCAP-D3, RBF1 and dCAP-D3 partially colocalize on polytene chromosomes, and RBF1 is required for efficient association of dCAP-D3 with chromatin. dCap-D3 mutants also exhibit chromatin condensation defects, and mutant alleles of dCap-D3 suppress cellular and developmental phenotypes induced by the overexpression of RBF1. Interestingly, this interaction is conserved between flies and humans. The re-expression of pRB into a pRB-deficient human tumor cell line promotes chromatin association of hCAP-D3 in a manner that depends on the LXCXE-binding cleft of pRB. These results uncover an unexpected link between pRB/RBF1 and chromatin condensation, providing a mechanism by which the functional inactivation of RB family members in human tumor cells may contribute to genome instability.