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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/29617

Title: The Role of Differential Phosphorylation of the Retinoblastoma Protein in Regulating Cell Proliferation and Elastogenesis
Authors: Sen, Sanjana
Advisor: Hinek, Aleksander
Department: Laboratory Medicine and Pathobiology
Keywords: Elastin
Retinoblastoma protein
Cell proliferation
Retinoblastoma control element
Cyclin E
Cyclin D
Costello Syndrome
Serine 780
Threonine 821
Elastin gene promoter
Issue Date: 25-Aug-2011
Abstract: Previous studies suggest that the IGF-I stimulates the elastin gene transcription through the unique responsive sequence on the elastin promoter, which is a putative retinoblastoma control element (RCE). This site interacts with (Sp)-family transcription factors whose delivery is mediated by the retinoblastoma protein (Rb). Since Rb (phosphorylated on serine 780) has been implicated in the initiation of the cell cycle, we speculated that a different phosphorylation of Rb might determine Rb involvement in elastogenesis. Obtained results demonstrated that, IGF-I-induced elastogenic signaling pathway in human dermal fibroblasts includes activation of cyclinE/cdk2 causing a site specific phosphorylation of Rb on threonine 821. This permits the sequestration of Sp1 by Rb before it could bind the elastin promoter, thereby allowing the elastin gene transcription. We also found that blocking of H-Ras in Costello syndrome fibroblasts (characterized by heightened proliferation and impaired elastogenesis), selectively down-regulated Rb phosphorylation on serine 780 and normalized impaired elastogenesis.
URI: http://hdl.handle.net/1807/29617
Appears in Collections:Master

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