Activated Rac1 regulates the degradation of I kappa B alpha and the nuclear translocation of STAT3-NF kappa B complexes in starved cancer cells

作者：Kim Sung Joo; Yoon Sarah^*

来源：Experimental and Molecular Medicine, 2016, 48(5): e231.

DOI：10.1038/emm.2016.17

In several human tumors, signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NF kappa B) are activated and interact; how these STAT3-NF kappa B complexes are transported to the nucleus is not fully understood. In this study, we found that Rac1 was activated in starved cancer cells and that activated Rac1 coexisted with STAT3 and NF kappa B. Rac1 knockdown and overexpression of the dominant-negative mutant Rac1N19 inhibited the degradation of I kappa B alpha, an inhibitor of NF kappa B. MG132, an inhibitor of the ubiquitin proteasome pathway, increased the amount of non-phosphorylated I kappa B alpha, but not serine-phosphorylated I kappa B alpha, indicating that I kappa B alpha degradation by Rac1 in starved cancer cells is independent of I kappa B alpha serine phosphorylation by IKK. Rac1 knockdown also inhibited the nuclear translocation of STAT3-NF kappa B complexes, indicating that this translocation requires activated Rac1. We also demonstrated that the mutant STAT3 Y705F could form complexes with NF kappa B, and these unphosphorylated STAT3-NF kappa B complexes translocated into the nucleus and upregulated the activity of NF kappa B in starved cancer cells, suggesting that phosphorylation of STAT3 is not essential for its translocation. To our knowledge, this is the first study demonstrating the crucial role of Rac1 in the function of STAT3-NF kappa B complexes in starved cancer cells and implies that targeting Rac1 may have future therapeutic significance in cancer therapy.

• 出版日期2016-5