Transient accumulation of retinoblastoma/E2F-1 protein complexes correlates with the onset of neuronal differentiation in the developing quail neural retina (original) (raw)
Related papers
2013
unchanged. This suggests that regulation of Rb expression during retina development occurs through posttranscriptional mechanisms. Retinoblastoma (Rb) protein has been implicated in the control of cell proliferation and malignant transformation in different cell types. To analyze ifs role as a promoter of cell growth arrest during development, we have studied the temporal pattern of Rb expression and its association with E2F-1 during embryogenesis of the quail neuroretina. During development of this neural organ, moat cells stop dividing and begin to differentiate at embryonic days E6 and E7, as indicated by the decline of cyclindependent kinase cdk2 and by an increased level of
The retinoblastoma gene family is differentially expressed during embryogenesis
Oncogene, 1997
We report dierential expression of the RB1 tumor suppressor gene and the homologous genes p107 and p130 during embryogenesis. Abundant RB1 transcripts were detected during neurogenesis, hematopoiesis, myogenesis, lens development and in the ganglion cell layer of the embryonic retina, prior to and during dierentiation. The expression pattern of RB1 mirrored the defects in RB1 mutant mice (RB 7/7). In the heart, lung, kidney and intestine, p107, but not RB1, was expressed. In the liver and the central nervous system p107 and RB1 were co-expressed, consistent with the accelerated cell death observed in RB 7/7 ; p107 7/7 double knockout mice. In the central nervous system, p107 expression was restricted to proliferating cells surrounding the ventricles, while RB1 was expressed in areas of both proliferating and dierentiating cells. In contrast to RB1 and p107, expression of p130 was low throughout embryogenesis. In situ hybridization and Western blot analyses showed that the expression of p107 and p130 was not markedly altered in RB 7/7 embryos compared to control littermates. Our results suggest that members of RB1 gene family have distinct, but overlapping roles in embryogenesis, with p107 and RB1 possibly having redundant functions in the central nervous system and liver.
Critical Reviews in Biochemistry and Molecular Biology, 1996
Genetic evidence from retinoblastoma patients and experiments describing the mechanism of cellular transformation by the DNA tumor viruses have defined a central role for the retinoblastoma protein (pRB) family of tumor suppressors in the normal regulation of the eukaryotic cell cycle. These proteins, pRB, p107, and p130, act in a cell cycle-dependent manner to regulate the activity of a number of important cellular transcription factors, such as the E2F-family, which in turn regulate expression of genes whose products are important for cell cycle progression. In addition, inhibition of E2F activity by the pRB family proteins is required for cell cycle exit after terminal differentiation or nutrient depletion. The loss of functional pRB, due to mutation of both RBI alleles, results in deregulated E2F activity and a predisposition to specific malignancies. Similarly, inactivation of the pRB family by the transforming proteins of the DNA tumor viruses overcomes cellular quiescence and prevents terminal differentiation by blocking the interaction of pRB, p107, and p130 with the E2F proteins, leading to cell cycle progression and, ultimately, cellular transformation. Together these two lines of evidence implicate the pRB family of negative cell cycle regulators and the E2F family of transcription factors as central components in the cell cycle machinery.
Phosphorylation of the retinoblastoma-related protein p130 in growth-arrested cells
Oncogene, 2000
The retinoblastoma family of proteins including pRB, p107 and p130 undergoes cell cycle dependent phosphorylation during the mid-G1 to S phase transition. This phosphorylation is dependent upon the activity of cyclin D/cdk4. In contrast to pRB and p107, p130 is phosphorylated during G0 and the early G1 phase of the cell cycle. We observed that p130 is speci®cally phosphorylated on serine and threonine residues in T98G cells arrested in G0 by serum deprivation or density arrest. Identi®cation of the phospho-serine and phosphothreonine residues revealed that most were clustered within a short co-linear region unique to p130, de®ned as the Loop. Deletion of the Loop region resulted in a change in the phosphorylation status of p130 under growth arrest conditions. Notably, deletion of the Loop did not aect the ability of p130 to bind to E2F-4 or SV40 Large T antigen, to induce growth arrest in Saos-2 cells, and to become hyperphosphorylated during the proliferative phase of the cell cycle. p130 undergoes speci®c G0 phosphorylation in a manner that distinguishes it from pRB and p107. Oncogene (2000) 19, 5116 ± 5122.
Regulation of the retinoblastoma protein-related p107 by G1 cyclin complexes
Genes & Development, 1995
The orderly progression through the cell cycle is mediated by the sequential activation of several cyclin/cyclin-dependent kinase (cdkl complexes. These kinases phosphorylate a number of cellular substrates, among which is the product of the retinoblastoma gene, pRb. Phosphorylation of pRb in late G~ causes the release of the transcription factor E2F from pRb, resulting in the transcriptional activation of E2F-responsive genes. We show here that phosphorylation of the pRb-related p107 is also cell cycle regulated, p107 is first phosphorylated at 8 hr following serum stimulation of quiescent fibroblasts, which coincides with an increase in cyclin D1 protein levels. Consistent with this, we show that a cyclin D1/cdk4 complex, but not a cyclin E/cdk2 complex, can phosphorylate p107 in vivo. Furthermore, phosphorylation of p107 can be abolished by the overexpression of a dominant-negative form of cdk4. Phosphorylation of p107 results in the loss of the ability to associate with E2F-4, a transcription factor with growth-promoting and oncogenic activity. A pl07-induced cell cycle block can be released by cyclin D1/cdk4 but not by cyclin E/cdk2. These data indicate that the activity of p107 is regulated by phosphorylation through D-type cyclins.
Compensation by tumor suppressor genes during retinal development in mice and humans
BMC Biology, 2006
The RB1 gene was the first tumor suppressor gene cloned from humans by studying genetic lesions in families with retinoblastoma. Children who inherit one defective copy of the RB1 gene have an increased susceptibility to retinoblastoma. Several years after the identification of the human RB1 gene, a targeted deletion of Rb was generated in mice. Mice with one defective copy of the Rb gene do not develop retinoblastoma. In this manuscript, we explore the different roles of the Rb family in human and mouse retinal development in order to better understand the speciesspecific difference in retinoblastoma susceptibility.