NF-κB-Dependent and -Independent (Moonlighting) IκBα Functions in Differentiation and Cancer.

Lluís Espinosa,Laura Marruecos

doi:10.3390/biomedicines9091278

Abstract

IκBα is considered to play an almost exclusive role as inhibitor of the NF-κB signaling pathway. However, previous results have demonstrated that SUMOylation imposes a distinct subcellular distribution, regulation, NF-κB-binding affinity and function to the IκBα protein. In this review we discuss the main alterations of IκBα found in cancer and whether they are (most likely) associated with NF-κB-dependent or NF-κB-independent (moonlighting) activities of the protein.

Highlights

IntroductionIκBα is considered to play an almost exclusive role as inhibitor of the NF-κB signaling pathway
Together, published data linking altered IκBα and cancer indicate that IκBα exerts an essential role in tissue homeostasis, and in the initiation, maintenance and progression of several types of cancer (Table 1)
We propose that IκBα alterations that impose constitutive activation of NF-κB may increase proliferation and invasion, and prevent cell apoptosis through transcriptional activation of specific NF-κB target genes (i.e., IL6, CyclinD1, cIAP)

Summary

Introduction

IκBα is considered to play an almost exclusive role as inhibitor of the NF-κB signaling pathway. Previous results have demonstrated that SUMOylation imposes a distinct subcellular distribution, regulation, NF-κB-binding affinity and function to the. In this review we discuss the main alterations of IκBα found in cancer and whether they are (most likely) associated with NF-κB-dependent (canonical) or NF-κBindependent (moonlighting) activities of the protein. (Moonlighting) IκBα Functions in Differentiation and Cancer

Altered Iκ

IκBα Activation and Functions κBα α Activation and Functions

Targeting NF-κ κBα α-Deficient Tumors

Findings

Conclusions