C-elegans class B synthetic multivulva genes act in G1 regulation
C-elegans class B synthetic multivulva genes act in G1 regulation
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DOI：
10.1016/s0960-9822(02)00844-8
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发表时间：
2002-06-04
期刊：
影响因子：
9.2
通讯作者：
van den Heuvel, S
中科院分区：
文献类型：
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作者：
Boxem, M;van den Heuvel, S
视网膜母细胞瘤基因家族的单个秀丽隐杆线虫成员 lin-35 Rb 最初被鉴定为合成的 Multivulva (synMuv) 基因 [1]。这些基因形成两个冗余类别，A 和 B，抑制异位外阴细胞命运诱导 [2, 3]。最近，我们证明 lin-35 Rb 还充当 G(1) 进展的负调节因子，并且可能是 cyd-1 Cyclin D 和 cdk-4 CDK4/6 的主要靶标 [4]。在这里，我们描述了其他几个 B 类 synMuv 基因的 G(1) 控制功能。我们发现 efl-1 E2F 负调节细胞周期进入，而 dpl-1 DP 似乎既充当正调节剂又负调节剂。此外，我们还发现了 lin-9 ALY 以及编码新蛋白的 lin-15B 和 lin-36 的负 G(1) 调节功能。 lin-35 Rb、efl-1 或 lin-36 的失活允许在没有 cyd-1/cdk-4 的情况下进入 S 期，并且与 cki-1 Cip/Kip RNAi 结合时增加异位细胞分裂。这些数据与 lin-35 Rb、efl-1 和 lin-36 作用于负调节 G(1) 进程的共同途径或复合物一致。相比之下，lin-15B 似乎与 lin-35 并行作用。我们的结果证明了在线虫中新型 G(1) 调节因子的遗传鉴定潜力。
The single C. elegans member of the retinoblastoma gene family, lin-35 Rb, was originally identified as a synthetic Multivulva (synMuv) gene [1]. These genes form two redundant classes, A and B, that repress ectopic vulval cell fate induction [2, 3]. Recently, we demonstrated that lin-35 Rb also acts as a negative regulator of G(1) progression and likely is the major target of cyd-1 Cyclin D and cdk-4 CDK4/6 [4]. Here,we describe G(1) control functions for several other class B synMuv genes. We found that efl-1 E2F negatively regulates cell cycle entry, while dpl-1 DP appeared to act both as a positive and negative regulator. In addition, we identified a negative G(1) regulatory function for lin-9 ALY, as well as lin-15B and lin-36, which encode novel proteins. Inactivation of lin-35 Rb, efl-1, or lin-36 allowed S phase entry in the absence of cyd-1/cdk-4 and increased ectopic cell division when combined with cki-1 Cip/Kip RNAi. These data are consistent with lin-35 Rb, efl-1, and lin-36 acting in a common pathway or complex that negatively regulates G(1) progression. In contrast, lin-15B appeared to act in parallel to lin-35. Our results demonstrate the potential for genetic identification of novel G(1) regulators in C. elegans.