Retinoblastoma protein: a central processing unit

Poznic, Miroslav

doi:10.1007/s12038-009-0034-2

Cited by 72 publications

(56 citation statements)

References 76 publications

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“…Although both AM23b and AM27b can regulate E2F1 expression, only AM23b significantly reduced the PS-induced Rb hypophosphorylation and cell cycle arrest. It is known that increases of Rb protein inhibits cell cycle progression and that Rb activities depend on its phosphorylation status (40). The hypophosphorylated Rb binds to E2F family proteins in a cell cycle-dependent manner to modulate proliferation (32,33).…”

Section: Discussionmentioning

confidence: 99%

Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth

Wang

Garmire

Young

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

158

132

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MicroRNAs (miRs) can regulate many cellular functions, but their roles in regulating responses of vascular endothelial cells (ECs) to mechanical stimuli remain unexplored. We hypothesize that the physiological responses of ECs are regulated by not only mRNA and protein signaling networks, but also expression of the corresponding miRs. EC growth arrest induced by pulsatile shear (PS) flow is an important feature for flow regulation of ECs. miR profiling showed that 21 miRs are differentially expressed (8 up-and 13 downregulated) in response to 24-h PS as compared to static condition (ST). The mRNA expression profile indicates EC growth arrest under 24-h PS. Analysis of differentially expressed miRs yielded 68 predicted mRNA targets that overlapped with results of microarray mRNA profiling. Functional analysis of miR profile indicates that the cell cycle network is highly regulated. The upregulation of miR-23b and miR-27b was found to correlate with the PS-induced EC growth arrest. Inhibition of miR-23b using antagomir-23b oligonucleotide (AM23b) reversed the PSinduced E2F1 reduction and retinoblastoma (Rb) hypophosphorylation and attenuated the PS-induced G1/G0 arrest. Antagomir AM27b regulated E2F1 expression, but did not affect Rb and growth arrest. Our findings indicate that PS suppresses EC proliferation through the regulation of miR-23b and provide insights into the role of miRs in mechanotransduction.cell cycle | shear | bioinformatics | gene regulation | mechanotransduction H emodynamic forces, e.g., stretch and shear stress, act constantly on the vascular endothelial cells (ECs) to modulate EC signaling, gene expression, and physiological functions (1). Atherosclerotic lesions in the arterial tree are found mainly at branch points, where blood flow is disturbed with a limited forwarding direction, but are generally spared at the straight parts of the arterial tree, where the flow is laminar with a large forwarding direction (2). Exposure of ECs to 24 h of steady laminar shear flow at 12 dyn/cm 2 (approximating the hemodynamic force in straight parts of arteries) leads to antiproliferative (3) and antiinflammatory (4) responses. In contrast, ECs exposed to disturbed flow, mimicking the hemodynamic force at branch points, exhibit opposite responses (5, 6). The laminar shear-induced EC growth arrest involves the expression of CDK inhibitors (e.g., p21 cip , p27 kip ), tumor suppressor p53, and retinoblastoma (Rb) hypophosphorylation (3, 7). Whereas there is considerable knowledge on mechanotransduction at protein and mRNA levels, there is little information on the role of microRNAs (miRs) in this process.miRs are small noncoding RNAs (∼21-25 nucleotides) that regulate gene expression by binding to target mRNAs to cause their degradation or translational repression (8). It is estimated that miRs regulate ∼30% of human protein-coding genes. More than 800 miRs have been identified in the human genome and registered in the Sanger miRBase. These small RNAs provide a powerful mechanism for posttranscriptional cont...

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Section: Discussionmentioning

confidence: 99%

Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth

Wang

Garmire

Young

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

158

132

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“…The retinoblastoma protein (pRb) is one of the key cell-cycle regulating proteins and its inactivation leads to neoplastic transformation and carcinogenesis (1). This protein regulates critical G1-to-S phase transition through interaction with the E2F family of cellcycle transcription factors repressing transcription of genes required for this cell-cycle check-point transition.…”

Section: Introductionmentioning

confidence: 99%

“…Its activity is regulated through network sensing intracellular and extracellular signals which block or permit phosphorylation (inactivation) of the Rb protein. The product of the RB gene is pRb, its function is to prevent the cell from entering S phase, whereas phosphorylated or mutated forms of this protein are incapable of arresting the cell in G1 phase of the cell cycle (1)(2)(3). Phosphorylation of pRB is mediated by complexes comprised of a D-type cyclin and cyclin dependent protein kinases (CDK4)/ (CDK6).…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical expression of pRb in pleomorphic adenoma and carcinoma ex pleomorphic adenoma

Tarakji¹

2011

Med Oral

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Objective: This study aimed to characterize alteration in the immunohistochemical expression of pRb in normal tissue of the salivary gland surrounding pleomorphic adenoma, the tumor cells of pleomorphic adenomas, and carcinoma arising in pleomorphic adenoma. Study Design: A selected series of 29 cases of pleomorphic adenomas, and 27 cases of carcinoma ex-pleomorphic adenoma (undifferentiated and adenocarcinoma types) were examined. Results: The results showed that pRb expression was negative in the components of normal tissue of the salivary gland surrounding pleomorphic adenoma. PRb expression in pleomorphic adenomas shows that 2 cases out of 29 (6.9 %) strongly expressed in the duct cells, 7/29 (24.1 %) cases showed moderate staining. pRb nuclear staining in myxochondroid was identified in 10/29 (34.5 %) cases of pleomorphic adenomas with weak staining, 6/29 (20.7 %) with moderate staining. pRb was strongly expressed in carcinoma cells in 19 out of 27 cases (70.4 %). Conclusion: This study suggests the alteration of pRb expression would increase from pleomorphic adenoma to carcinoma arising in pleomorphic adenomas (6.9 % versus 70.4 %).

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“…Compelling evidence indicates that apoptosis is instrumental in glaucoma, retinitis pigmentosa, cataract, retinoblastoma, retinal ischemia, diabetic retinopathy and several eye infections caused by viruses, bacteria, fungi and some protozoans (Kaneda et al 1999;Vemuganti et al 2004;Cottet and Schorderet 2009;Zhang et al 2010;Poznic M 2009;Barber et al 2011;Pinazo-Durán et al 2013). In contrast, we are just beginning to understand the role of autophagy in ocular diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Multiplication of these viruses subverts the physiological regulation of apoptotic cell demise Blaho 2007 and2009). Apoptosis, termed type I programmed cell death, is a type of cell deletion characterized by stereotypic cytomorphological changes, such as nuclear compaction, DNA fragmentation to nucleosomesized fragments and cell shrinkage resulting in cellular breakdown into membrane-bound apoptotic bodies.…”

Section: Introductionmentioning

confidence: 99%

Herpes simplex virus types 1 and 2 modulate autophagy in SIRC corneal cells

et al. 2014

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Autophagy and apoptosis function as important early cellular defense mechanisms in infections and other diseases. The outcome of an infection is determined by a complex interplay between the pathogenic microorganism and these intracellular pathways. To better understand the cytopathogenicity of Herpes simplex virus types 1 and 2 (HSV-1 and -2), we studied the effect of these viruses on the autophagic and apoptotic processes in the SIRC corneal cell line. Infection with the KOS strain of HSV-1 and a wild-type strain of HSV-2 enhanced autophagosome formation, triggered cytoplasmic acidification, increased LC3B lipidation and elevated the ratio of apoptotic cells. The autophagy inhibitor bafilomycin A1 triggered a significant increase in the apoptotic responses of HSV-1-and HSV-2-infected cells. Thus, both HSV types affect autophagy and apoptosis in a coordinated fashion, and autophagy plays cytoprotective role in HSV-infected cells via antagonizing apoptosis. Together these data implicate autophagy in the pathogenic mechanism of herpetic keratitis.[Petrovski G, Pásztor K, Orosz L, Albert R, Mencel E, Moe MC, Kaarniranta K, Facskó A and Megyeri K 2014 Herpes simplex virus types 1 and 2 modulate autophagy in SIRC corneal cells.

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Retinoblastoma protein: a central processing unit

Cited by 72 publications

References 76 publications

Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth

Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth

Immunohistochemical expression of pRb in pleomorphic adenoma and carcinoma ex pleomorphic adenoma

Herpes simplex virus types 1 and 2 modulate autophagy in SIRC corneal cells

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