Regulation in Cell Cycle via p53 and PTEN Tumor Suppressors

Yasuko Kitagishi*, Satoru Matsuda*, Akari Minami, Yuna Ono, Atsuko Nakanishi and Yasunori Ogura

Regulation in Cell Cycle via p53 and PTEN Tumor Suppressors. One of the target effectors of p53 transcription factor is the Phosphatase and Tensin homologue deleted on chromosome 10 (PTEN) which has protein phosphatase activity and lipid phosphatase activity that antagonizes PI3K activity. Cells that lack PTEN have constitutively higher levels of PIP3 and activated downstream targets. Both p53 and PTEN are tumor suppressors that act by inhibiting cell cycle progression and promoting apoptosis.

Germline mutations in p53 and PTEN cause Li-Fraumeni syndrome and Cowden syndrome, respectively. The p53 cooperates with PTEN, which might be an essential blockage in development of cancers. PTEN protects p53 from MDM2- mediated degradation, whereas p53 can enhance the transcription of PTEN. This review summarizes the function of PTEN and p53 in cell cycle regulation. We will also discuss the role of PTEN signaling through its interaction with p53 and MDM2 pathways for the potential implications in the cell cycle regulation.

Mechanisms of cell arrest in cell cycle are predominantly governed by p53 tumor suppressor1 that is a transcription factor. The p53 protein is able to induce G1 arrest of the cell cycle by trans-activating several downstream molecules.  The p53 is at a midpoint of cellular signaling networks that are activated by stress signals including DNA damages.

Recent studies have revealed a functional ubiquitin ligase for tumor suppressors play a pivotal role in tumor cell survival. They may regulate the stability of key tumor suppressors. Mutations found in genes such as p53 and PTEN have emerged as high penetrance susceptibility genes and are clinically relevant for determination of cancer risk. In addition, there are multiple nodes of crosstalk between PI3K/AKT/PTEN and p53 signaling .

Cancer Stud Mol Med Open J. 2014; 1(1): 1-7. doi: 10.17140/CSMMOJ-1-101