A tumor suppressor Retinoblastoma1 is essential for embryonic development in the sea urchin

A tumor suppressor Retinoblastoma1 is essential for embryonic development in the sea urchin
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DOI:
10.1002/dvdy.113
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发表时间:
2019-10-01
影响因子:
2.5
通讯作者:
Yajima, Mamiko
Yajima, Mamiko
中科院分区:
生物学3区
文献类型:
--
作者:
Fernandez-Nicolas, Ana;Xu, Derek;Yajima, Mamiko

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背景胚胎细胞和癌细胞具有对其功能非常重要的各种细胞特性。因此,有人提出,在这些原本不同的细胞类型中可能存在类似的调节机制。结果为了探索调节性胚胎细胞与癌细胞的根本区别,我们报道了在海胆胚胎发生过程中,肿瘤抑制蛋白视网膜母细胞瘤蛋白(Rb1)和生殖系因子Vasa的精细平衡对于细胞的适当增殖和体细胞的分化是重要的。Rb1基因的敲除阻碍了胚胎的发育并诱导了Vasa在整个胚胎中的积累,而它的过度表达导致了一个具有分化的体型结构的较小的胚胎。这些结果表明,在发育过程中,Rb1蛋白的滴定水平对于细胞增殖和分化的适当平衡可能是必不可少的。另一方面,VASA基因下调或过度表达分别降低或增加了Rb1蛋白的表达。结论VasA蛋白对Rb1蛋白有正向调节作用,而Rb1蛋白对VasA蛋白有负性调节作用,两者在体细胞中起平衡作用。这一机制可能提供对细胞增殖和分化的精细控制,这是调节胚胎发育所必需的。
Background Embryonic cells and cancer cells share various cellular characteristics important for their functions. It has been thus proposed that similar mechanisms of regulation may be present in these otherwise disparate cell types. Results To explore how regulative embryonic cells are fundamentally different from cancerous cells, we report here that a fine balance of a tumor suppressor protein Retinoblastoma1 (Rb1) and a germline factor Vasa are important for proper cell proliferation and differentiation of the somatic cells during embryogenesis of the sea urchin. Rb1 knockdown blocked embryonic development and induced Vasa accumulation in the entire embryo, while its overexpression resulted in a smaller-sized embryo with differentiated body structures. These results suggest that a titrated level of Rb1 protein may be essential for a proper balance of cell proliferation and differentiation during development. Vasa knockdown or overexpression, on the other hand, reduced or increased Rb1 protein expression, respectively. Conclusions Taken together, it appears that Vasa protein positively regulates Rb1 protein while Rb1 protein negatively regulates Vasa protein, balancing the act of these two antagonistic molecules in somatic cells. This mechanism may provide a fine control of cell proliferation and differentiation, which is essential for regulative embryonic development.