Non genomic loss of function of tumor suppressors in CML: BCR-ABL promotes I kappa B alpha mediated p53 nuclear exclusion

作者：Crivellaro Sabrina; Panuzzo Cristina; Carra Giovanna; Volpengo Alessandro; Crasto Francesca; Gottardi Enrico; Familiari Ubaldo; Papotti Mauro; Torti Davide; Piazza Rocco; Redaelli Sara; Taulli Riccardo; Guerrasio Angelo; Saglio Giuseppe; Morotti Alessandro^*

来源：Oncotarget, 2015, 6(28): 25217-25225.

DOI：10.18632/oncotarget.4611

• NF-kappa B
• I kappa B alpha
• chronic myeloid leukemia
• p53
• tumor suppressor

Tumor suppressor function can be modulated by subtle variation of expression levels, proper cellular compartmentalization and post-translational modifications, such as phosphorylation, acetylation and sumoylation. The non-genomic loss of function of tumor suppressors offers a challenging therapeutic opportunity. The reactivation of a tumor suppressor could indeed promote selective apoptosis of cancer cells without affecting normal cells. The identification of mechanisms that affect tumor suppressor functions is therefore essential. In this work, we show that BCR-ABL promotes the accumulation of the NFKBIA gene product, I kappa B alpha, in the cytosol through physical interaction and stabilization of the protein. Furthermore, BCR-ABL/I kappa B alpha complex acts as a scaffold protein favoring p53 nuclear exclusion. We therefore identify a novel BCR-ABL/I kappa B alpha/p53 network, whereby BCR-ABL functionally inactivates a key tumor suppressor.

• 出版日期2015-9-22