Abstract
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 G1 progression and likely is the major target of cyd-1 Cyclin D and cdk-4 CDK4/6 [4]. Here, we describe G1 control functions for several other class B synMuv genes. We found that eft-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 G1 regulatory function for lin-9 ALY, as well as lin-15B and lin-36, which encode novel proteins. Inactivation of lin-35 Rb, eft-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, eft-1, and lin-36 acting in a common pathway or complex that negatively regulates G1 progression. In contrast, lin-15B appeared to act in parallel to lin-35. Our results demonstrate the potential for genetic identification of novel G1 regulators in C. elegans.
| Original language | English |
|---|---|
| Pages (from-to) | 906-911 |
| Number of pages | 6 |
| Journal | Current Biology |
| Volume | 12 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 4 Jun 2002 |
| Externally published | Yes |
Bibliographical note
Funding Information:We are indebted to C. Ceol, H.R. Horvitz, V. Ambros, M. Park, and M. Krause for reagents and strains. We thank N. Dyson, C. Voisine, and members of the van den Heuvel laboratory for helpful discussions and critical reading of the manuscript. The Caenorhabditis Genetic Center, supported by the National Institutes of Health (NIH), provided several strains used in these studies. S.v.d.H is supported by grants from the NIH. M.B. is a recipient of a pre-doctoral fellowship from the Boehringer Ingelheim Fonds.
Funding
We are indebted to C. Ceol, H.R. Horvitz, V. Ambros, M. Park, and M. Krause for reagents and strains. We thank N. Dyson, C. Voisine, and members of the van den Heuvel laboratory for helpful discussions and critical reading of the manuscript. The Caenorhabditis Genetic Center, supported by the National Institutes of Health (NIH), provided several strains used in these studies. S.v.d.H is supported by grants from the NIH. M.B. is a recipient of a pre-doctoral fellowship from the Boehringer Ingelheim Fonds.