Expression of the E2F and retinoblastoma families of proteins during neural differentiation

Kusek, Judith; Greene, Robert M.; Pisano, M. Michele

doi:10.1016/s0361-9230(00)00447-0

Cited by 27 publications

(26 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To test whether the down-regulation of Axin occurs in vivo as well as during P19 EC cell differentiation, the Axin level was compared in the brains of 13.5 dpc mouse embryos (which contain many undifferentiated neuronal precursor cells) versus brains of 1-month-old postnatal mice (which contain more differentiated neurons). The level of the neuron-specific marker ␤III-tubulin was increased during that period, as shown by others (55), whereas the Axin level was reduced (Fig. 2E).…”

Section: Differential Expression Of Wnt Signaling Components Duringsupporting

confidence: 79%

Ectopic Expression of Axin Blocks Neuronal Differentiation of Embryonic Carcinoma P19 Cells

Lyu

Costantini

Jho

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Axin regulates Wnt signaling through down-regulation of ␤-catenin. To test the role of Wnt signaling in neuronal differentiation, embryonal carcinoma P19 cells (P19 EC), which can be stimulated to differentiate into a neuron-like phenotype in response to retinoic acid (RA), were used. Reverse transcription-PCR and Western blot analysis showed that Axin is expressed in undifferentiated cells, whereas the level is clearly reduced during RA-induced neuronal differentiation. Interestingly, Axin levels were not reduced during endodermal differentiation of P19 EC cells and F9 EC cells by RA, suggesting that the reduction of the Axin level is a specific property of neuronal differentiation. Western analysis showed that the cytoplasmic level of ␤-catenin increased during neuronal differentiation of P19 EC cells. Indirect immunofluorescence with ␤-catenin antibody showed that the localization of ␤-catenin was changed from membrane in undifferentiated cells to nuclei in neuronal P19 EC cells. Induced expression of Axin during endodermal and early neuronal differentiation, using the Tet-On system, did not block normal differentiation. However, maintenance of the Axin level blocked neuronal differentiation and inhibited expression of a neuron-specific marker protein, ␤III-tubulin. Also, ectopic induction of a ␤-catenin signaling inhibitor, ICAT, inhibited expression of ␤III-tubulin. In contrast, addition of Wnt-3A-conditioned medium during the neuronal differentiation period enhanced the expression of ␤III-tubulin. Overall, our data show that Wnt-3a/canonical ␤-catenin signaling through the downregulation of Axin may play an important role in neuronal differentiation.

show abstract

Section: Differential Expression Of Wnt Signaling Components Duringsupporting

confidence: 79%

Ectopic Expression of Axin Blocks Neuronal Differentiation of Embryonic Carcinoma P19 Cells

Lyu

Costantini

Jho

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Given the tissue-restricted, developmentally regulated expression patterns of E2Fs and Rb family members in vivo shown by us ( Fig. 1A and 6A) and others (23,29), the degree to which different Rb proteins can functionally compensate for one another may vary depending on the cellular context. However, results of gene expression profiling on RNA isolated from single-or double-null hearts (30) demonstrate that even in cardiac muscle, where Rb and p130 clearly have overlapping roles, they do have distinct gene targets and unique functions may exist for each family member particularly in the context of physiological stress.…”

Section: Discussionmentioning

confidence: 91%

Overlapping Roles of Pocket Proteins in the Myocardium Are Unmasked by Germ Line Deletion of p130 plus Heart-Specific Deletion of Rb

MacLellan

Garcia

et al. 2005

Molecular and Cellular Biology

115

104

View full text Add to dashboard Cite

The pocket protein family of tumor suppressors, and Rb specifically, have been implicated as controlling terminal differentiation in many tissues, including the heart. To establish the biological functions of Rb in the heart and overcome the early lethality caused by germ line deletion of Rb, we used a Cre/loxP system to create conditional, heart-specific Rb-deficient mice. Mice that are deficient in Rb exclusively in cardiac myocytes (CRb L/L ) are born with the expected Mendelian distribution, and the adult mice displayed no change in heart size, myocyte cell cycle distribution, myocyte apoptosis, or mechanical function. Since both Rb and p130 are expressed in the adult myocardium, we created double-knockout mice (CRb L/L p130 ؊/؊ ) to determine it these proteins have a shared role in regulating cardiac myocyte cell cycle progression. Adult CRb L/L p130 ؊/؊ mice demonstrated a threefold increase in the heart weight-to-body weight ratio and showed increased numbers of bromodeoxyuridine-and phosphorylated histone H3-positive nuclei, consistent with persistent myocyte cycling. Likewise, the combined deletion of Rb plus p130 up-regulated myocardial expression of Myc, E2F-1, and G 1 cyclin-dependent kinase activities, synergistically. Thus, Rb and p130 have overlapping functional roles in vivo to suppress cell cycle activators, including Myc, and maintain quiescence in postnatal cardiac muscle.

show abstract

“…A few evidences support this hypothesis. pRb2/p130 upregulation during development and maturation of nervous system, including the retina, has been reported (Kastner et al, 1998;Kusek et al, 2001). Nothing is known about p73 role in modeling the precise retinal architecture, but it has been reported that, if p53 responds to immediate genotoxic stress, its homologue p73 would participate in the cell homeostasis of neuronal tissue along its development and differentiation (Douc-Rasy et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Genetic and epigenetic alterations of RB2/p130 tumor suppressor gene in human sporadic retinoblastoma: implications for pathogenesis and therapeutic approach

et al. 2005

View full text Add to dashboard Cite

Human retinoblastoma occurs in two forms (familial and sporadic) both due to biallelic mutation of the RB1/p105 gene even if its loss is insufficient for malignancy. We have recently reported that loss of expression of the retinoblastoma-related protein pRb2/p130 correlates with low apoptotic index, suggesting that RB2/p130 gene could be involved in retinoblastoma. Mutational analysis of RB2/ p130 in primary tumors showed a tight correlation between Exon 1 mutations and pRb2/p130 expression level in sporadic retinoblastoma. These mutations are located within a CpG-enriched region prone to de novo methylation. Analysis of RB2/p130 methylation status revealed that epigenetic events, most probably consequent to the Exon 1 mutations, determined the observed phenotype. Treatment of Weri-Rb1 cell line by 5-AzadC induced an increase in expression level of pRb2/p130, E2F1, p73 and p53. Overall, our results highlight a crucial role of epigenetic events in sporadic retinoblastoma, which opens a perspective for new therapeutic approaches.

show abstract

Expression of the E2F and retinoblastoma families of proteins during neural differentiation

Cited by 27 publications

References 80 publications

Ectopic Expression of Axin Blocks Neuronal Differentiation of Embryonic Carcinoma P19 Cells

Ectopic Expression of Axin Blocks Neuronal Differentiation of Embryonic Carcinoma P19 Cells

Overlapping Roles of Pocket Proteins in the Myocardium Are Unmasked by Germ Line Deletion of p130 plus Heart-Specific Deletion of Rb

Genetic and epigenetic alterations of RB2/p130 tumor suppressor gene in human sporadic retinoblastoma: implications for pathogenesis and therapeutic approach

Contact Info

Product

Resources

About