Elevated cyclic AMP levels induce a rapid block in the mid-G1 phase of the cell cycle in B-lymphoid Reh cells, accompanied by a transient block in G2. The retinoblastoma (Rb) gene product has been implicated as a key regulator of eukaryotic cell growth. The Rb protein enforces its growth-suppressive effect in early G1, where it is underphosphorylated and firmly bound in the nucleus. A possible ...

Elongation factor, RNA polymerase II, 2 (ELL2) is expressed and regulated by androgens in the prostate. ELL2 and ELL-associated factor 2 (EAF2) form a stable complex, and their orthologs in Caenorhabditis elegans appear to be functionally similar. In C. elegans, the EAF2 ortholog eaf-1 was reported to interact with the retinoblastoma (RB) pathway to control development and fertility in worms. B...

Retinoblastoma (RB; encoded by RB1) is a tumor suppressor that is frequently disrupted in tumorigenesis and acts in multiple cell types to suppress cell cycle progression. The role of RB in tumor progression, however, is poorly defined. Here, we have identified a critical role for RB in protecting against tumor progression through regulation of targets distinct from cell cycle control. In analy...

Re-expression of a tumor suppressor in tumor cells that lack it is an effective way to study its functional activities. However, because tumor cells contain multiple mutations, tumor suppressor functions that are dependent on (an)other regulators are unlikely to be identified by its re-expression alone if the other regulators are also mutated. In this study, we show that re-expression of retino...

Autophagy is a protective mechanism that renders cells viable in stressful conditions. Emerging evidence suggests that this cellular process is also a tumor suppressor pathway. Previous studies showed that cyclin-dependent kinase inhibitors (CDKI) induce autophagy. Whether retinoblastoma protein (RB), a key tumor suppressor and downstream target of CDKIs, induces autophagy is not clear. Here, w...

The retinoblastoma tumor suppressor protein (RB) is targeted for inactivation in the majority of human tumors, underscoring its critical role in attenuating cellular proliferation. RB inhibits proliferation by repressing the transcription of genes that are essential for cell cycle progression. To repress transcription, RB assembles multiprotein complexes containing chromatin-modifying enzymes, ...

Rohon Beard (RB) cells are embryonic primary sensory neurons that are removed by programmed cell death during larval development in zebrafish. RB somatosensory functions are taken over by neurons of the dorsal root ganglia (DRG), suggesting that RB cell death may be triggered by the differentiation of these ganglia, as has been proposed to be the case in Xenopus. However, here we show that the ...

The retinoblastoma protein Rb has antiproliferative and antiapoptotic functions. Our previous studies have shown that certain apoptotic signals can inactivate Rb via the p38 pathway. Here we show that Rb associates with the apoptosis signal-regulating kinase ASK1 in response to specific apoptotic signals. An LXCXE motif on ASK1 was required for Rb binding; this correlated with increased E2F1 tr...

Sarcomas have been modeled in mice by the expression of specific fusion genes in mesenchymal stem cells (MSC), supporting the concept that MSCs might be the target initiating cell in sarcoma. In this study, we evaluated the potential oncogenic effects of p53 and/or retinoblastoma (Rb) deficiency in MSC transformation and sarcomagenesis. We derived wild-type, p53(-/-), Rb(-/-), and p53(-/-)Rb(-/...