Open Access. Powered by Scholars. Published by Universities.®

Life Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 4 of 4

Full-Text Articles in Life Sciences

Characterizing The Role Of The Retinoblastoma Protein Lxcxe Binding Cleft In Cellular Senescence And Tumor Suppression, Srikanth Talluri Jul 2013

Characterizing The Role Of The Retinoblastoma Protein Lxcxe Binding Cleft In Cellular Senescence And Tumor Suppression, Srikanth Talluri

Electronic Thesis and Dissertation Repository

The Retinoblastoma protein (pRB) is a key regulator of the cell cycle and is functionally inactivated in most cancers. pRB has been proposed to utilize simultaneous interactions with E2F transcription factors and chromatin regulatory proteins to repress transcription and block cell cycle progression. The goal of this study is to characterize the physiological role of pRB interactions with chromatin regulatory proteins. I used gene targeted mice carrying point mutations in the murine Rb1 gene (Rb1∆L) that specifically disrupt pRB’s LXCXE binding cleft, and thereby its ability to interact with chromatin regulatory proteins while leaving its ability to bind ...


Expression Of Growth Arrest And Dna Damage Protein 45-Alpha (Gadd45-Alpha) And The Ccaat/Enhancer Binding Protein-Delta (C/Ebp-Delta) In Fishes Exposed To Heat And Hypoxia, Daniel Omar Hassumani Mar 2013

Expression Of Growth Arrest And Dna Damage Protein 45-Alpha (Gadd45-Alpha) And The Ccaat/Enhancer Binding Protein-Delta (C/Ebp-Delta) In Fishes Exposed To Heat And Hypoxia, Daniel Omar Hassumani

Dissertations and Theses

The cellular stress response (CSR) is one of the most highly conserved mechanisms among all organisms. Cellular stress can be defined as damage or the threat of damage to proteins, macromolecules and/or DNA. The response to damage can involve cell cycle regulation, protein chaperoning, DNA repair or, if macromolecular damage is too severe, apoptotic mechanisms can be initiated. This thesis details experiments that were designed to examine the cellular response to non-lethal environmental stressors at the protein level, using two fish species as study models. Two proteins that can cause cell cycle arrest and apoptosis mechanisms were examined. Expression ...


Arx Influences Cortical Function By Regulating Progenitor Cell Proliferation, Jacqueline Christine Simonet Jan 2013

Arx Influences Cortical Function By Regulating Progenitor Cell Proliferation, Jacqueline Christine Simonet

Publicly Accessible Penn Dissertations

Mutations in the Aristaless-related homeobox (ARX) gene are found in a spectrum of epilepsy and X-linked intellectual disability disorders in children. During development Arx is expressed in pallial ventricular zone (VZ) progenitor cells which give rise to the excitatory projection neurons of the cortex. Arx-/Y mice were shown to have decreased proliferation in the cortical VZ resulting in smaller brains; however, the basis for this reduced proliferation was not established. To determine the role of ARX on cell cycle dynamics in cortical progenitor cells, we generated cerebral cortex specific Arx mouse mutants (cKO). The loss of pallial Arx resulted ...


The Multifunctional Protein Daxx: Studies Of Its Biology And Regulation, And Discovery Of A Novel Function, Trisha Agrawal Jan 2013

The Multifunctional Protein Daxx: Studies Of Its Biology And Regulation, And Discovery Of A Novel Function, Trisha Agrawal

Publicly Accessible Penn Dissertations

Daxx, a multifunctional protein with a diverse set of proposed functions, is ubiquitously expressed and highly conserved through evolution. A primarily nuclear protein, Daxx is able to regulate apoptosis, transcription, and cellular proliferation. Despite many studies into the function of Daxx, its precise role in the cell remains enigmatic. Herein, evidence is presented to expand upon the known anti-apoptotic function of Daxx, to establish Daxx as a novel molecular chaperone, and to further its repertoire of transcriptional targets. As an apoptotic inhibitor, Daxx is known to regulate p53 by stabilizing its main negative regulator, Mdm2, via formation of a ternary ...