Graduation Year

2005

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Biochemistry and Molecular Biology

Major Professor

William G. Kerr, Ph.D.

Keywords

p53, E2F, EGFR, RNAi, AKT

Abstract

LRBA (LPS Responsive Beige-like Protein Kinase A anchor) gene expression is induced by the mitogen LPS and is a member of the WBW gene family member which is comprised of genes that are involved in cellular proliferation and differentiation. This work provides evidence for the over-expression of LRBA in certain cancers, and that LRBA promoter activity and endogenous LRBA mRNA levels are negatively regulated by the tumor suppressor p53 and positively regulated by E2F transactivators. Furthermore, we demonstrate that inhibition of LRBA expression or function leads to decreased proliferation of cancer cells and that LRBA plays a role in the EGFR signal transduction pathway. In addition to the findings of LRBA's role in carcinogenesis, this work also shows evidence of the knockdown of the SH2-containing Inositol 5' Phosphatase (SHIP) in both mouse and human cells. Furthermore, we provide evidence that SHIP-1 is involved in the AKT signal transduction pathway in human Natural Killer cells.

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