Chaves-Ferreira Miguel, Krenn Gerald, Vasseur Florence, Barinov Aleksandr, Gonçalves Pedro, Azogui Orly, Cumano Ana, Li Zhi, Pellegrini Sandra, Rocha Benedita, Laderach Diego
INSERM, U 1020, U1151 - CNRS, UMR 8253, Institut Necker Enfants Malades, Faculté de Médecine Paris Descartes, 25, Rue du Dr Roux, Cedex 15, Paris, France.
Present addresses: Instituto de Medicina Molecular, Avenida Prof. Egas Moniz, 1649-028, Lisbon, Portugal.
Biol Direct. 2016 Apr 29;11:21. doi: 10.1186/s13062-016-0122-9.
The family of D cyclins has a fundamental role in cell cycle progression, but its members (D1, D2, D3) are believed to have redundant functions. However, there is some evidence that contradicts the notion of mutual redundancy and therefore this concept is still a matter of debate.
Our data show that the cyclin D1 is indispensable for normal hematopoiesis. Indeed, in the absence of D1, either in genetic deficient mice, or after acute ablation by RNA interference, cyclins D2 and D3 are also not expressed preventing hematopoietic cell division and differentiation at its earliest stage. This role does not depend on the cyclin box, but on the carboxyl regulatory domain of D1 coded by exons 4-5, since hematopoietic differentiation is also blocked by the conditional ablation of this region.
These results demonstrate that not all functions of individual D cyclins are redundant and highlight a master role of cyclin D1 in hematopoiesis.
D型细胞周期蛋白家族在细胞周期进程中起基本作用,但其成员(D1、D2、D3)被认为具有冗余功能。然而,有一些证据与相互冗余的概念相矛盾,因此这一概念仍是一个有争议的问题。
我们的数据表明,细胞周期蛋白D1对正常造血至关重要。事实上,在缺乏D1的情况下,无论是在基因缺陷小鼠中,还是在通过RNA干扰进行急性消融后,细胞周期蛋白D2和D3也不表达,从而在最早阶段阻止造血细胞分裂和分化。这一作用不依赖于细胞周期蛋白盒,而是依赖于由外显子4-5编码的D1的羧基调节域,因为该区域的条件性消融也会阻断造血分化。
这些结果表明,并非单个D型细胞周期蛋白的所有功能都是冗余的,并突出了细胞周期蛋白D1在造血中的主要作用。