Abstract
The nuclear factor kappa B (NF-κB) plays vital role in the immune system by regulating innate and adaptive immunity, development and survival of lymphocytes, and lymphoid organogenesis. All known NF-κB activators converge on the IkappaB kinase (IKK) complex to activate the canonical and non-canonical NF-κB pathways the IKK complex contains two catalytic subunits (IKKα and IKKβ) and a regulatory subunit NEMO/IKKγ that regulates the canonical NF-κB pathway, whereas IKKα regulates the non-canonical pathway the process of IKKα activation and its role in the regulation of canonical NF-κB activation remain elusive the canonical pathway is rapidly activated and produces a potent inflammatory response to bacterial and viral infections as well as different types of stress; however, uncontrolled NF-κB activation can lead to autoimmune diseases and cancers therefore, to keep the inflammatory response in check, elaborate negative regulatory mechanisms operate to terminate NF-κB activation at multiple levels by de novo synthesis of NF-κB inhibitory proteins, and orchestration of protein ubiquitination and deubiquitination the NF-κB target genes, IκBα and A20, play critical roles in termination of the active canonical NF-κB pathway. In this review, we discuss our recent findings describing a novel function for IKKα in nucleating the ubiquitin-editing enzyme A20 complex, a major negative regulator of canonical NF-κB signaling. Consistently with an inhibitory function of IKKα, it is targeted by the human T-cell leukemia virus 1 (HTLV-1) oncoprotein, Tax, to prevent assembly of the A20 complex to maintain persistent NF-κB activation that promotes transformation and survival of virus-transformed cells.
| Original language | English |
|---|---|
| Pages (from-to) | 166-171 |
| Number of pages | 6 |
| Journal | Immunologic Research |
| Volume | 57 |
| Issue number | 1-3 |
| DOIs | |
| State | Published - Dec 1 2013 |
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Keywords
- Autoimmunity
- IKK
- Innate immunity
- Ubiquitin NF-κB
ASJC Scopus subject areas
- Immunology
Cite this
A20-mediated negative regulation of canonical NF-κB signaling pathway. / Pujari, Rajeshree; Hunte, Richard; Khan, Wasif; Shembade, Noula.
In: Immunologic Research, Vol. 57, No. 1-3, 01.12.2013, p. 166-171.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A20-mediated negative regulation of canonical NF-κB signaling pathway
AU - Pujari, Rajeshree
AU - Hunte, Richard
AU - Khan, Wasif
AU - Shembade, Noula
PY - 2013/12/1
Y1 - 2013/12/1
N2 - The nuclear factor kappa B (NF-κB) plays vital role in the immune system by regulating innate and adaptive immunity, development and survival of lymphocytes, and lymphoid organogenesis. All known NF-κB activators converge on the IkappaB kinase (IKK) complex to activate the canonical and non-canonical NF-κB pathways the IKK complex contains two catalytic subunits (IKKα and IKKβ) and a regulatory subunit NEMO/IKKγ that regulates the canonical NF-κB pathway, whereas IKKα regulates the non-canonical pathway the process of IKKα activation and its role in the regulation of canonical NF-κB activation remain elusive the canonical pathway is rapidly activated and produces a potent inflammatory response to bacterial and viral infections as well as different types of stress; however, uncontrolled NF-κB activation can lead to autoimmune diseases and cancers therefore, to keep the inflammatory response in check, elaborate negative regulatory mechanisms operate to terminate NF-κB activation at multiple levels by de novo synthesis of NF-κB inhibitory proteins, and orchestration of protein ubiquitination and deubiquitination the NF-κB target genes, IκBα and A20, play critical roles in termination of the active canonical NF-κB pathway. In this review, we discuss our recent findings describing a novel function for IKKα in nucleating the ubiquitin-editing enzyme A20 complex, a major negative regulator of canonical NF-κB signaling. Consistently with an inhibitory function of IKKα, it is targeted by the human T-cell leukemia virus 1 (HTLV-1) oncoprotein, Tax, to prevent assembly of the A20 complex to maintain persistent NF-κB activation that promotes transformation and survival of virus-transformed cells.
AB - The nuclear factor kappa B (NF-κB) plays vital role in the immune system by regulating innate and adaptive immunity, development and survival of lymphocytes, and lymphoid organogenesis. All known NF-κB activators converge on the IkappaB kinase (IKK) complex to activate the canonical and non-canonical NF-κB pathways the IKK complex contains two catalytic subunits (IKKα and IKKβ) and a regulatory subunit NEMO/IKKγ that regulates the canonical NF-κB pathway, whereas IKKα regulates the non-canonical pathway the process of IKKα activation and its role in the regulation of canonical NF-κB activation remain elusive the canonical pathway is rapidly activated and produces a potent inflammatory response to bacterial and viral infections as well as different types of stress; however, uncontrolled NF-κB activation can lead to autoimmune diseases and cancers therefore, to keep the inflammatory response in check, elaborate negative regulatory mechanisms operate to terminate NF-κB activation at multiple levels by de novo synthesis of NF-κB inhibitory proteins, and orchestration of protein ubiquitination and deubiquitination the NF-κB target genes, IκBα and A20, play critical roles in termination of the active canonical NF-κB pathway. In this review, we discuss our recent findings describing a novel function for IKKα in nucleating the ubiquitin-editing enzyme A20 complex, a major negative regulator of canonical NF-κB signaling. Consistently with an inhibitory function of IKKα, it is targeted by the human T-cell leukemia virus 1 (HTLV-1) oncoprotein, Tax, to prevent assembly of the A20 complex to maintain persistent NF-κB activation that promotes transformation and survival of virus-transformed cells.
KW - Autoimmunity
KW - IKK
KW - Innate immunity
KW - Ubiquitin NF-κB
UR - http://www.scopus.com/inward/record.url?scp=84891486850&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84891486850&partnerID=8YFLogxK
U2 - 10.1007/s12026-013-8463-2
DO - 10.1007/s12026-013-8463-2
M3 - Article
C2 - 24242761
AN - SCOPUS:84891486850
VL - 57
SP - 166
EP - 171
JO - Immunologic Research
JF - Immunologic Research
SN - 0257-277X
IS - 1-3
ER -