Function for NF-kB in neuronal survival: Regulation by atypical protein kinase C

Abstract

Activation of the transcription factor nuclear factor kappa B (NF-kB) has been intensely studied in the past several years due to its role as an inducible regulator of inflammation, apoptosis, transformation, and oncogenesis. Recently, increasing evidence supports a role for NF-kB in regulation of anti-apoptotic gene expression and promotion of cell survival (May and Ghosh [1999] Science 284:272-273). Studies in the past 5 years have provided evidence that NF-kB regulates neuronal survival as well. Moreover, atypical protein kinase (aPKC) has been shown to play a novel role in modulating the NF-kB pathway. In this review, I focus on neurons and the factors that contribute to regulation of NF-kB via aPKC.

Loss of the Polarity Protein PAR3 Activates STAT3 Signaling via an Atypical Protein Kinase C (aPKC)/NF-κB/Interleukin-6 (IL-6) Axis in Mouse Mammary Cells

“…aPKC/ and aPKC interact with and activate multiple components of the NF-B pathway (39). aPKC/-mediated activation of NF-B induces IL-6 production in prostate cancer (23), and silencing of PAR3 can activate NF-B signaling in human intestinal epithelial cells (40).…”

Roles for NF-κB in nerve cell survival, plasticity, and disease

“…14 These molecules can activate NF-kB through coupling to kinase cascades including calcium/calmodulindependent kinase II, 15 Akt 16,17 and protein kinase C 18 ( Figure 2). One or more of the latter signaling pathways is likely to account for the high constitutive activity of NF-kB in neurons compared to nonexcitable cells.…”

Dual role for p75NTR signaling in survival and cell death: Can intracellular mediators provide an explanation?

“…IB proteins are rapidly phosphorylated by the IKK complex and then degraded by the ubiquitin-proteosome pathway. Following IB degradation, NF-B translocates into the nucleus and activates a wide spectrum of genes involved in immunity, inflammation, and neuronal survival (reviewed in: Kopp and Ghosh, 1994;O'Neill and Kaltschmidt, 1997;Wooten, 1999).…”

“…In addition, overexpression of the NF-B protein c-Rel in sympathetic neurons and RelA and p50 in trigeminal neurons is sufficient to promote neuronal survival in the absence of NGF (Maggirwar et al, 1998;Hamanoue et al, 1999). NF-B is important for sustaining the survival of mature neurons and in neurodegenerative diseases (reviewed in: O'Neill and Kaltschmidt, 1997;Wooten, 1999). In the p75 NTR -mediated NF-B activation pathway, TRAF6 was shown to be recruited to the p75 NTR upon treatment with the neurotrophins (Khursigara et al, 1999).…”

“…Moreover, aPKCs protect neural cells against apoptosis (Xie et al, 2000) induced by amyloid beta-peptide, which is known to play a major role in the neurodegenerative process in Alzheimer's disease (reviewed in Wooten, 1999). Overexpression of wild-type or activated aPKC was sufficient to trigger NF-B activation .…”