Signal-dependent and -independent Degradation of Free and NF-κB-bound IκBα*
By M. Pando, Inder M. Verma. Journal of Biological Chemistry, 2000
123 citations recorded by the source corpus.
A family of inhibitory IκB molecules regulates the activation of the transcription factor NF-κB. One member of the IκB family, IκBα, plays a major role in the rapid signal-induced activation of NF-κB. IκBα itself is transcriptionally regulated by NF-κB allowing for a tight autoregulatory loop that is both sensitive to and rapidly influenced by NF-κB activating stimuli. For this pathway to remain primed both for rapid activation of NF-κB in the presence of signal and then to suppress NF-κB activation once that signal is removed, IκBα must be exquisitely regulated. The regulation of IκBα is mainly accomplished through phosphorylation, ubiquitination, and subsequent degradation. The mechanism(s) that regulate IκBα degradation needs to be able to target IκBα for degradation in both its NF-κB bound and free states in the cell. In this study, we utilize a full-length IκBα mutant that is unable to associate to RelA/p65. We show that the signal-induced IκB kinase (IKK) phosphorylation sites on IκBα can only significantly influence the regulation of signal-dependent but not signal-independent turnover of IκBα. We also demonstrate that the constitutive carboxyl-terminal casein kinase II phosphorylation sites are necessary for the proper regulation of both signal-dependent and -independent turnover of IκBα. These findings further elucidate how the phosphorylation of IκBα influences the complex regulatory mechanisms involved in maintaining a sensitive NF-κB pathway.
Subfields: Cancer Research, Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/925cabb6439b0133f6a690d4841b035b711c8d99
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Citations in the corpus
- Translational Repression Mediates Activation of Nuclear Factor Kappa B by Phosphorylated Translation Initiation Factor 2 (2004, background): “The plausibility of the latter explanation is supported by evidence for the existence of multiple pools of IB in cells (25, 33 , 41).”
- Biophysical characterization of the free IκBα ankyrin repeat domain in solution (2004, background): “Physiological implications of the dynamic state of I B Free I B displays a short half-life in the cell (Pando and Verma 2000).”
- Mathematical model of NF- κB regulatory module (2004, background): “ion rate Fitted , free IkBa protein degradation Pando and Verma (2000) tion (complexed to NF-kB) Pando and Verma (2000)”