Role of Translationally Controlled Tumor Protein in Cancer Progression

Figure 1

Mechanistic diagram showing the effect of abnormal regulation of TCTP/Cdc25C/Cdk1 pathway in HCC development. (Upper panel) Under the normal mitotic progression, Cdc25C activates Cdk1 by the dephosphorylation of Thr14 and Tyr15 in Cdk1. The level of active Cdk1 is a key factor for maintaining the mitotic state and functions as a key switch for cell division. (Lower panel) During the HCC development, TCTP is overexpressed in over 40% of HCC cases. Overexpression of TCTP promotes the ubiquitin-proteasome degradation of Cdc25C, which leads to the failure in the dephosphorylation of Cdk1 on Tyr15 and decreases Cdk1 activity. As a consequence, the sudden drop of Cdk1 activity in mitosis induces a faster mitosis exit and chromosome missegregation, which leads to aneuploidy and CIN, finally causing cancer development.