lin-35

We present evidence that lin-35 promotes germ cell apoptosis by repressing the expression of ced-9, an anti-apoptotic C. elegans gene that is orthologous to the human proto-oncogene BCL2.

However, as the suppression by lin-35 Rb is not complete, cyd-1 and cdk-4 probably have additional targets.

However, as the suppression by lin-35 Rb is not complete, cyd-1 and cdk-4 probably have additional targets.

Finally, we demonstrate that lin-35, dpl-1 and efl-2, but not efl-1, function either downstream of or in parallel to cep-1 p53 (also known as TP53) and egl-1 BH3-only to cause DNA damage-induced germ cell apoptosis.

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 results demonstrate that lin-35 Rb is an important negative regulator of G1/S progression and probably a downstream target for cyd-1 and cdk-4.

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.

We propose that lin-35, fzr-1, and lin-23 function redundantly to control cell cycle progression through the regulation of cyclin levels.

Based on genetic and phenotypic analyses, this role for lin-35 in pharyngeal morphogenesis appears to be distinct from its cell cycle-related functions. lin-35 and ubc-18 may act in concert to regulate the levels of one or more critical targets during C. elegans development.

We suggest that a rate limiting role for cki-1 Cip/Kip rather than lin-35 Rb explains the lack of cell-cycle phenotype of lin-35 mutant animals.

We also demonstrate a specific function for xnp-1 together with lin-35 or hpl-2 in the control of transgene expression, a process known to be dependent on chromatin remodelling.

We also provide genetic and phenotypic evidence to support the model that PHA-1, a novel protein, and UBC-18, a ubiquitin-conjugating enzyme that we have previously shown to function with lin-35 during pharyngeal development, act in parallel pathways to regulate the activity of a common cellular target.

Here we show that lin-35/Rb, efl-1/E2F, and other SynMuv B genes negatively regulate a component of the anaphase-promoting complex or cyclosome (APC/C).

The C. elegans APC/C gene mat-3/APC8 has been defined by temperature-sensitive embryonic lethal alleles that strongly affect germline meiosis and mitosis but only weakly affect somatic development.

The tumor suppressor daf-18/PTEN inhibits IIS to suppress starvation-induced abnormalities, but we show that it also acts independently of IIS via lin-35/Rb, another tumor suppressor, to suppress such abnormalities.

However, when metformin was administered in the presence of high glucose, the lifespan of lin-35 worms was clearly longer compared to N2 worms.

According to our findings, act-1 and cdc-42 were effective in accurately normalizing the levels of gene expression in N2 and lin-35. act-1 and cdc-42 also displayed the most consistent expression patterns, therefore they were utilized to standardize expression level of sgk-1.

According to our findings, act-1 and cdc-42 were effective in accurately normalizing the levels of gene expression in N2 and lin-35. act-1 and cdc-42 also displayed the most consistent expression patterns, therefore they were utilized to standardize expression level of sgk-1.

Using a genetic approach to identify genes that may function redundantly with lin-35, we have isolated a mutation in the C. elegans psa-1 gene. lin-35; psa-1 double mutants display severe developmental defects leading to early larval arrest and adult sterility.

Partial inactivation of specific spliceosome components revealed further similarities with lin-35 Rb functions in cell-cycle control, transgene expression and restricted expression of germline granules.