Beta-catenin effect in NF-kB transcriptional activity

CIUCCI S, ERLEJMAN A, MAZAIRA G, GALIGNIANA MD

Congreso; LXVI Reunión Anual de SAIC; 2022

SAIC

β-catenin plays an important role in a multitude of developmental and homeostatic processes, its associate with E- cadherin in cell-cell adhesion and is a key nuclear effector of canonical Wnt signalling participating in diverse physiological processes such a proliferation, differentiation, apoptosis, migration, invasion and tissue homeostasis. Another key factor in signalling is NF-κB. NF-κB (p65/p50 heterodimer) is a transcriptional factor that participates in the induction of a wide variety of genes involve in inflammatory responses, cell development, programmed cell death, proliferation control, and tumorigenesis. In unstimulated cells NF-κB is normally retained in the cytosol in an inactive form due to their association with the inhibitory factor IκB. Stimulation with specific inducers activates IκB kinase (IKK) that phospholylates IκB generating its degradation by proteosome. Hence, NF-κB can translocate to the nucleus where it plays its role as a transcriptional factor. On the other hand, our group had demonstrated that the immunophilins FKBP51 and FKBP52 play an important role in NF-κB shutting to the nucleus and its transcriptional response, being FKBP51 an inhibitory factor while FKBP52 is a strong activator. In the present work we evaluated the potential effect of β-catenin on NF-κB transcriptional activity. First, we measured NF-κB activity by a reporter gene assay, HEK293T cells were transfected with increasing doses of β-catenin (0,5 ? 1 ? 1,5 ug) and stimulated or not with PMA for 7 hours. Surprisingly, we found that in unstimulated and stimulated cells β-catenin supress NF-κB transcriptional activity in a dose response manner. Then, we investigated if this inhibitory effect could be abolished by FKBP52. HEK293T cells were transfected with β-catenin (0,5 ug) and increasing doses of FKBP52 (0,5- 1- 1,5 ug) and transcriptional activity was measured by luciferase assay. We found that even the lowest dose could displace this inhibitory effect in stimulated states. In summary, in this study we found a new possible NF-κB regulator that could help us to understand more NF- κB regulation.