Epidermal Growth Factor-induced Rapid Retinoblastoma Phosphorylation at Ser780 and Ser795 Is Mediated by ERK1/2 in Small Intestine Epithelial Cells

Guo, Jun; Sheng, George; Warner, Brad W.

doi:10.1074/jbc.m504583200

Cited by 55 publications

(43 citation statements)

References 39 publications

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“…Hyperphosphorylation at serine 780, serine 807/ 811, and threonine 821/826 appears to be involved in the disruption of E2F binding to Rb [16]. Therefore, the phospho-Rb-positive cells in our study may not be capable of binding to E2F.…”

Section: Discussionmentioning

confidence: 46%

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The Significance of p53 and Retinoblastoma Pathways in Canine Hemangiosarcoma

Yonemaru

Sakai

Murakami

et al. 2007

The Journal of Veterinary Medical Science

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ABSTRACT. To investigate whether inactivation of the p53 and retinoblastoma (Rb) protein pathways contributes to the development of canine hemangiosarcoma (HSA), we examined immunohistochemically the expression of p53, Rb, phosphorylated Rb (phospho-Rb), p16, and cyclin D1 in 39 spontaneous canine HSAs and 10 hemangiomas. In addition, mutations in the p53 gene were analyzed by polymerase chain reaction (PCR)-single-stranded conformation polymorphism and PCR direct sequencing; furthermore, we quantified cyclin D1 mRNA by semiquantitative real-time reverse transcription-PCR. Positive immunoreactivity for p53 was observed in 17.9% of HSAs. However, mutations were not detected in these cases. The labeling indices for Rb, phospho-Rb, and cyclin D1 were markedly higher in all HSAs than in hemangiomas. Of the 7 cases with cyclin D1-positive immunoreactivity, 4 overexpressed cyclin D1 mRNA (to a level more than 10-fold higher than that of GAPDH mRNA). The p16 protein was clearly detected in all hemangiomas; however, 82% of the neoplastic cells in HSA showed a loss of or low immunoreactivity. These results suggest that alteration of the p16-cyclin D1-Rb pathway, rather than the p53 pathway, may be associated with the pathogenesis of canine HSA. KEY WORDS: canine hemangiosarcoma, cyclin D1, p16, p53, Rb.

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Section: Discussionmentioning

confidence: 46%

“…The significance of Rb phosphorylation at different sites is suggested by the observation that Rb function may be modulated according to the location at which it is phosphorylated [16]. Hyperphosphorylation at serine 780, serine 807/ 811, and threonine 821/826 appears to be involved in the disruption of E2F binding to Rb [16].…”

Section: Discussionmentioning

confidence: 99%

The Significance of p53 and Retinoblastoma Pathways in Canine Hemangiosarcoma

Yonemaru

Sakai

Murakami

et al. 2007

The Journal of Veterinary Medical Science

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“…In fact, Guo et al (2005) demonstrated that in prototype small intestine crypt stem cells the activity of RB is regulated at multiple levels. The acute loss of intestinal regions triggers mitogenic signals to the intestinal crypt cells to grow taller villi and deepen the crypts in order to increase the area of remaining absorptive and digestive mucosa.…”

Section: Small Intestine Crypt Stem Cellsmentioning

confidence: 99%

“…The acute loss of intestinal regions triggers mitogenic signals to the intestinal crypt cells to grow taller villi and deepen the crypts in order to increase the area of remaining absorptive and digestive mucosa. Among the different mitogens, the EGF-mediated signaling appears to play a major role in this process (Guo et al, 2005). The treatment of RIEC-6 cell cultures (a model of small intestine crypt stem cells) with EGF induces a sustained proliferation that is associated with a heavy pRb phosphorylation.…”

Section: Small Intestine Crypt Stem Cellsmentioning

confidence: 99%

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The retinoblastoma gene is involved in multiple aspects of stem cell biology

2006

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Genetic programs controlling self-renewal and multipotentiality of stem cells have overlapping pathways with cell cycle regulation. Components of cell cycle machinery can play a key role in regulating stem cell self-renewal, proliferation, differentiation and aging. Among the negative regulators of cell cycle progression, the RB family members play a prominent role in controlling several aspects of stem cell biology. Stem cells contribute to tissue homeostasis and must have molecular mechanisms that prevent senescence and hold 'stemness'. RB can induce senescence-associated changes in gene expression and its activity is downregulated in stem cells to preserve self-renewal. Several reports evidenced that RB could play a role in lineage specification of several types of stem cells. RB has a role in myogenesis as well as in cardiogenesis. These effects are not only related to its role in suppressing E2F-responsive genes but also to its ability to modulate the activity of tissue-specific transcription factors. RB is also involved in adipogenesis through a strict control of lineage commitment and differentiation of adipocytes as well in determining the switch between brown and white adipocytes. Also, hematopoietic progenitor cells utilize the RB pathway to modulate cell commitment and differentiation. In this review, we will also discuss the role of the other two RB family members: Rb2/p130 and p107 showing that they have both specific and overlapping functions with RB gene.

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EGFR signaling suppresses osteoblast differentiation and inhibits expression of master osteoblastic transcription factors Runx2 and osterix

Zhu

Shimizu

Zhang

et al. 2011

J of Cellular Biochemistry

100

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The epidermal growth factor receptor (EGFR) and its ligands regulate key processes of cell biology, such as proliferation, survival, differentiation, migration, and tumorigenesis. We previously showed that EGFR signaling pathway is an important bone regulator and it primarily plays an anabolic role in bone metabolism. In this study, we demonstrated that EGF-like ligands strongly inhibited osteoblast differentiation and mineralization in several lines of osteoblastic cells. Real-time RT-PCR and promoter reporter assays revealed that EGF-like ligands suppressed the expression of both early and late bone marker genes at the transcriptional level in the differentiating osteoblasts via an EGFR-dependent manner. This inhibitory effect of EGFR signaling was not dependent on its mitogenic activity. Furthermore, we demonstrated that EGFR signaling reduced the expression of two major osteoblastic transcription factors Runx2 (type II) and Osterix in osteoblast differentiating cells. EGFR-induced decrease in Runx2 transcriptional activity was confirmed by Runx2 reporter and chromatin immunoprecipitation assays. EGFR signaling increased the protein amounts of transcription corepressors HDAC4 and 6 and overexpression of HDAC4 decreased Runx2 amount in differentiating osteoblasts, implying that HDACs contribute to the down-regulation of Runx2 by EGFR. Moreover, activation of EGFR in undifferentiated osteoprogenitors attenuated the expression of early bone markers and Osterix and decreased Runx2 protein amounts. Together with our previous data that EGFR stimulates osteoprogenitor proliferation and that blocking EGFR activity in osteoblast lineage cells results in fewer osteoprogenitors and osteopenic phenotype, we conclude that EGFR signaling is important for maintaining osteoprogenitor population at an undifferentiated stage.

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Epidermal Growth Factor-induced Rapid Retinoblastoma Phosphorylation at Ser780 and Ser795 Is Mediated by ERK1/2 in Small Intestine Epithelial Cells

Cited by 55 publications

References 39 publications

The Significance of p53 and Retinoblastoma Pathways in Canine Hemangiosarcoma

The Significance of p53 and Retinoblastoma Pathways in Canine Hemangiosarcoma

The retinoblastoma gene is involved in multiple aspects of stem cell biology

EGFR signaling suppresses osteoblast differentiation and inhibits expression of master osteoblastic transcription factors Runx2 and osterix

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