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Open Access Publications from the University of California

GPCR and RhoA-Mediated Transcriptional Regulation

  • Author(s): Yu, Olivia
  • Advisor(s): Heller Brown, Joan
  • et al.

The ability of a subset of G-protein coupled receptors (GPCRs) to activate RhoA

endows them with unique growth regulatory properties. Dysregulation of steps in this

signaling process subvert the normal control of RhoA activation and may underlie pathophysiological changes in gene expression and downstream responses such as glioblastoma tumor cell growth or fibrosis. Chapter 1 serves as an introduction to this thesis and provides background information on our current understanding of RhoA signaling and transcriptional responses. Chapter 2 describes the protein cysteine-rich angiogenic inducer 61 (CCN1) as a downstream target gene of RhoA and MRTF-A signaling that contributes to protection from ischemia/reperfusion injury in the mouse heart. Chapters 3 and 4 examine the role of two transcriptional pathways that are activated through GPCRs and RhoA, one utilizing the transcriptional co-activator MRTF-A and SRF, the other the transcriptional co-activator YAP and TEAD. Chapter 3 focuses on their unique pathways of activation and convergent effects on gene regulation. Chapter 4 identifies genes regulated uniquely or commonly via YAP and MRTF-A, defines their differential roles and that of their downstream target genes in regulating cell invasion, migration, adhesion, and proliferation, as well as, effects of their genetic deletion on growth and lethality of glioblastoma tumors in the in vivo mouse brain. Finally, Chapter 5 summarizes and identifies remaining questions and extension of studies presented in previous chapters.

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