STUDYING THE ROLE OF CPSF6 AS A MUTANT P53 EFFECTOR IN TUMOR AGGRESSIVENESS

ALBANO HERALDO TENAGLIA; ARROYO MARÍA NICOL; JAVIER GIRARDINI; CARLA MARIA BORINI ETICHETTI

Córdoba

Congreso; 52th Annual Meeting Argentine Society for Biochemistry and Molecular Biology (SAIB); 2016

SAIB

Most human cancers inactivate the tumor suppressor p53 through missense mutations, leading to the expression of full-length pointmutant proteins. Besides losing the tumor suppressor function of the wt protein, p53 mutants may acquire novel activities that promoteaggressiveness and metastasis. Understanding the molecular mechanisms underlying mutant p53 oncogenic function may help toidentify molecular ways and targets for cancer treatment. We have previously found that Pin1 cooperates with mutant p53 to alter geneexpression in breast cancer cells. In particular, both proteins cooperate to induce the expression of 10 genes (Pin1/mutant p53signature) whose expression is associated with the development of aggressive breast tumors. Among them we found CPSF6, whichcodes for a 68 kDa protein, belonging to the CFIm processing factor that regulates mRNA polyadenilation. Although several aspects ofCFIm function in mRNA processing were described, little is known regarding the role of CPSF6 in human cancer. In order to identifybiological effects of CPSF6 that may cooperate with tumor progression, we used zebrafish embryos as biosensors to study theconsequences of Cpsf6 overexpression in vivo. As a mean to investigate the mechanisms regulating the expression of DaniorerioCpsf6, we analyzed the expression of Cpsf6 deletions lacking the N-terminal, C-terminal and proline-rich domains.