Date Approved


Document Type


Degree Name

Master of Science in Molecular Pathology and Immunology


Molecular Biology


Graduate School of Biomedical Sciences

First Advisor

Salvatore Caradonna, PhD

Committee Member 1

Grant Gallagher, PhD

Committee Member 2

Joseph Nickels, PhD


Protein Phosphatase 2; Carcinogenesis; Tumor Suppressor Proteins; Molecular Targeted Therapy


Cancer Biology | Cell Biology | Laboratory and Basic Science Research | Life Sciences | Medicine and Health Sciences | Molecular Biology | Neoplasms | Therapeutics


The oncogene cancerous inhibitor of protein phosphatase 2A (CIP2A) has been shown to promote oncogenesis through numerous protein-protein interactions. CIP2A was initially found to be a direct inhibitor of the PP2A tumor suppressor protein; however, new research has demonstrated that CIP2A can act independently of PP2A through protein-protein interactions resulting in deregulation of the cell cycle and the development of therapeutic drug resistance, tumorigenesis, and cell proliferation. It has been shown that leucine rich repeat containing 59 protein (LRRC59) binds to and is required for the nuclear translocation of CIP2A, thereby making this interaction a target for drug therapy. Thus, we hypothesize that inhibiting the CIP2A-LRRC59 interaction will eliminate CIP2A nuclear translocation and, ultimately, its function. Paramount to this hypothesis is understanding the physical interactions between LRRC59 and CIP2A. We performed truncation studies to define the domains within LRRC59 that interact with CIP2A. Moreover, we explored if CIP2A acts as a scaffold to recruit a series of proteins involved in regulating G2-M transition. NIMA-related kinase 2 (Nek2) is a key regulator in centrosome segregation. Nek2 acts through the phosphorylation of its substrates, including the mitotic regulators Hec1 and Sgo1, both of which have been suggested to associate with CIP2A. Thus, we asked if CIP2A acts as a tether required for the Nek2-Hec1-Sgo1 complex to promote mitotic progression in cancer cells. Co-immunoprecipitation methods were used to investigate these protein-protein interactions. Our studies have verified known interaction, and our preliminary data suggests that CIP2A does, indeed, act as an oncogenic-promoting scaffold.