Polo-like kinase 1 in cell division and its implicatioin for cancer therapy

Xiaoxiao Shawn Liu, Purdue University

Abstract

Cells are the basic building blocks for all organisms and multiply through cell division. In order to divide, one cell needs to duplicate its chromosomes and equally separate the duplicated chromosomes through a process called the cell cycle. This process has to be accurately regulated to maintain genome integrity, and dysregulation of cell cycle may result in severe diseases such as cancer. The research presented in this dissertation studies the role of Polo-like kinase 1 (Plk1), a critical regulator of cell division, and its implication for cancer therapy. G2 and S phase expressed protein 1 (GTSE-1), was identified as a substrate of Plk1, and characterized. Plk1-mediated phosphorylation of GTSE-1 was demonstrated to be essential for the inactivation of the tumor suppressor p53 during G2 DNA damage checkpoint recovery. To understand the role of Plk1 during tumorigenesis, a prostate cancer mouse model was used to show that knock-out of the tumor suppressor Pten can result in the elevated expression of Plk1. Plk1 is critical for Pten-depleted cells to adapt to the mitotic stress, characterized by chromosome misalignment phenotype. Another substrate of Plk1, Sgt1, was identified and characterized to illustrate how Plk1 promotes the kinetochore-microtubule attachment and thus to facilitate proper chromosome alignment. This study advances the knowledge of cell cycle regulation by Plk1, and demonstrates the facilitative role of Plk1 during tumorigenesis, providing a strategy to target Plk1 for cancer therapy.

Degree

Ph.D.

Advisors

Liu, Purdue University.

Subject Area

Biology|Cellular biology|Biochemistry|Oncology

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