One strategy to block NF-κB activation is through the transfer of genes that code for proteins shown to suppress NF-κB activation. The most direct target is IκBα. IκBα mutation at specific phosphorylation sites (Ser32 and Ser36 replaced to alanine) and ubiquitination sites (Lys21 and Lys22 mutated to arginine) results in a nondegradable form of IκBα. This results in a stable cytoplasmic pool of IκBα, thereby preventing NF-κB activation [130–132]. Injecting a nonphosphorylatable form of IκBα into bone marrow macrophages has been shown to inhibit osteoclastogenesis and block bone resorption [133]. Additionally, specific C-terminal serine-to-alanine mutations are sometimes included to reduce the constitutive turnover of IκBα [134]. These super-repressor forms of IκBα can still interact with NF-κB dimers to keep the dimers in the cytoplasm permanently [132, 134, 135]. Such molecules have been used succesfully to inhibit NF-κB activity and to study its role in tumor development [136, 137] and to sensitize tumor cells to apoptosis-inducing agents [134, 135]. Inhibiting NF-κB through the expression of an IκBα super-repressor (IκBαSR) has also been used to sensitize chemoresistant tumors to TNFα- and CPT-11-induced
