Integrating cell-signalling pathways with NF-κB and IKK function

  title={Integrating cell-signalling pathways with NF-$\kappa$B and IKK function},
  author={Neil D Perkins},
  journal={Nature Reviews Molecular Cell Biology},
  • N. Perkins
  • Published 2007
  • Biology
  • Nature Reviews Molecular Cell Biology
Nuclear factor (NF)-κB and inhibitor of NF-κB kinase (IKK) proteins regulate many physiological processes, including the innate- and adaptive-immune responses, cell death and inflammation. Disruption of NF-κB or IKK function contributes to many human diseases, including cancer. However, the NF-κB and IKK pathways do not exist in isolation and there are many mechanisms that integrate their activity with other cell-signalling networks. This crosstalk constitutes a decision-making process that… 
Crosstalk in NF-κB signaling pathways
NF-κB transcription factors are critical regulators of immunity, stress responses, apoptosis and differentiation. A variety of stimuli coalesce on NF-κB activation, which can in turn mediate varied
NF-κB and the cell cycle.
An updated review of the current state of knowledge about integration of NF-κB activity with cell cycle regulation is provided, including newly characterized direct and indirect target genes in addition to the mechanisms through which NF- κB itself can be regulated by the cell cycle.
Targeting IKK and NF-κB for Therapy.
The diverse and complex roles of NF-κB subunits in cancer
If the NF-κB pathway is to be properly exploited as a target for both anticancer and anti-inflammatory drugs, it is appropriate to reconsider the complex roles of the individual NF-σκB subunits.
NF-κ Ba nd the cell cycle
An updated review of the current state of knowledge about integration of NF-κB activity with cell cycle regulation, including newly characterized direct and indirect target genes in addition to the mechanisms through which NF- κB itself can be regulated by the cell cycle are provided.
Roles of NF-kappaB in health and disease: mechanisms and therapeutic potential.
The NF-kappaB (nuclear factor kappaB) family of transcription factors are involved in a myriad of activities, including the regulation of immune responses, maturation of immune cells, development of
The role of the NFκB signalling pathway in cancer
The development of chemical inhibitors that block NFκB activation acting either directly on IKKs or on the proteosome machinery has shown antitumour and proapoptotic activity both in preclinical and clinical studies.
NF-κB Signaling Pathways
The authors summarize the findings and discuss their significance with respect to survival or death in the nervous system of nuclear factor-κB.
NF-κB in Cellular Senescence and Cancer Treatment
This review discusses implications of the NF-κB signaling pathway in cancer, and emphasizes the connection of NF-σB with cellular senescence as a response to chemotherapy, and presents examples how distinct oncogenic network contexts surrounding NF-KKB produce fundamentally different treatment outcomes in aggressive B-cell lymphomas.


Ubiquitin signalling in the NF-κB pathway
Several enzymes involved in the ubiquitination and deubiquitination of signalling proteins that mediate IKK activation through a degradation-independent mechanism are revealed.
IKK/NF-κB signaling: balancing life and death – a new approach to cancer therapy
Inhibition of IKK-driven NF-kappaB activation offers a strategy for treatment of different malignancies and can convert inflammation- induced tumor growth to inflammation-induced tumor regression.
Shaping the nuclear action of NF-κB
The NF-κB/REL family of transcription factors pivotally control the inflammatory and immune responses, as well as other genetic programmes that are central to cell growth and survival. The
Activators and target genes of Rel/NF-κB transcription factors
It is argued that NF-κB functions more generally as a central regulator of stress responses and pairing stress responsiveness and anti-apoptotic pathways through the use of a common transcription factor may result in increased cell survival following stress insults.
Interactions of NF-κB with chromatin: the art of being at the right place at the right time
It is becoming increasingly apparent that in addition to this required activation step, both recruitment of NF-κB to target genes and NF-σκB-induced transcriptional events after recruitment are actively controlled.
The tumour suppressor CYLD negatively regulates NF-κB signalling by deubiquitination
CYLD, a tumour suppressor that is mutated in familial cylindromatosis, interacts with NEMO, the regulatory subunit of IKK, strengthening the notion that ubiquitination is involved in IKK activation by TRAFs and suggesting that CYLD functions in this process.
The NF-κB-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease
It is shown that further delineating the mechanisms by which NF-κB promotes cell survival might hold the key to developing new highly effective therapies for treatment of widespread human diseases.
NF-κB Is Essential for Induction of CYLD, the Negative Regulator of NF-κB
A novel autoregulatory feedback pathway through which activation of NF-κB by TNF-α and bacterium nontypeable Haemophilus influenzae (NTHi) induces CYLD that in turn leads to the negative regulation of NF -κB signaling is revealed.