The NF-kappaB signalling pathway in human diseases: from incontinentia pigmenti to ectodermal dysplasias and immune-deficiency syndromes - PubMed (original) (raw)
Review
. 2002 Oct 1;11(20):2371-5.
doi: 10.1093/hmg/11.20.2371.
Affiliations
- PMID: 12351572
- DOI: 10.1093/hmg/11.20.2371
Review
The NF-kappaB signalling pathway in human diseases: from incontinentia pigmenti to ectodermal dysplasias and immune-deficiency syndromes
Asma Smahi et al. Hum Mol Genet. 2002.
Abstract
The transcription factor NF-kappaB regulates the expression of numerous genes controlling the immune and stress responses, inflammatory reaction, cell adhesion, and protection against apoptosis. Incontinentia pigmenti (IP) is the first genetic disorder to be ascribed to NF-kappaB dysfunction. IP is an X-linked dominant genodermatosis antenatally lethal in males. A complex rearrangement of the NEMO (NF-kappaB essential modulator) gene accounts for 85% of IP patients, and results in undetectable NEMO protein and absent NF-kappaB activation. On the other hand, hypohidrotic/anhidrotic ectodermal dysplasia (HED/EDA) has been ascribed to at least three genes also involved in NF-kappaB activation: ectodysplasin (EDA1), EDA-receptor (EDAR) and EDAR-associated death domain (EDARADD). During hair follicle morphogenesis, EDAR is activated by ectodysplasin, and uses EDARADD as an adapter to build a signal transducing complex that leads to NF-kappaB activation. Hence, several forms of HED/EDA also result from impaired activation of the NF-kappaB cascade. Finally, hypomorphic NEMO mutations have been found to cause anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID), whilst stop codon mutations cause a more severe phenotype associating EDA-ID with osteopetrosis and lymphoedema (OL-EDA-ID). The immunological and infectious features observed in patients result from impaired NF-kappaB signalling, including cellular response to LPS, IL-1beta, IL-18, TNF-alpha, Tlr2 and CD40 ligand. Consistently, mouse knockout models have shown the essential role of NF-kappaB in the immune, inflammatory and apoptotic responses. Unravelling the molecular bases of other forms of EDA not associated with mutations in NEMO will possibly implicate other components of the NF-kappaB signalling pathway.
Similar articles
- EDA-ID and IP, two faces of the same coin: how the same IKBKG/NEMO mutation affecting the NF-κB pathway can cause immunodeficiency and/or inflammation.
Fusco F, Pescatore A, Conte MI, Mirabelli P, Paciolla M, Esposito E, Lioi MB, Ursini MV. Fusco F, et al. Int Rev Immunol. 2015;34(6):445-59. doi: 10.3109/08830185.2015.1055331. Epub 2015 Aug 13. Int Rev Immunol. 2015. PMID: 26269396 Review. - X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling.
Döffinger R, Smahi A, Bessia C, Geissmann F, Feinberg J, Durandy A, Bodemer C, Kenwrick S, Dupuis-Girod S, Blanche S, Wood P, Rabia SH, Headon DJ, Overbeek PA, Le Deist F, Holland SM, Belani K, Kumararatne DS, Fischer A, Shapiro R, Conley ME, Reimund E, Kalhoff H, Abinun M, Munnich A, Israël A, Courtois G, Casanova JL. Döffinger R, et al. Nat Genet. 2001 Mar;27(3):277-85. doi: 10.1038/85837. Nat Genet. 2001. PMID: 11242109 - Immunodeficiency in Two Female Patients with Incontinentia Pigmenti with Heterozygous NEMO Mutation Diagnosed by LPS Unresponsiveness.
Ohnishi H, Kishimoto Y, Taguchi T, Kawamoto N, Nakama M, Kawai T, Nakayama M, Ohara O, Orii K, Fukao T. Ohnishi H, et al. J Clin Immunol. 2017 Aug;37(6):529-538. doi: 10.1007/s10875-017-0417-3. Epub 2017 Jul 12. J Clin Immunol. 2017. PMID: 28702714 - Osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency in a boy and incontinentia pigmenti in his mother.
Dupuis-Girod S, Corradini N, Hadj-Rabia S, Fournet JC, Faivre L, Le Deist F, Durand P, Döffinger R, Smahi A, Israel A, Courtois G, Brousse N, Blanche S, Munnich A, Fischer A, Casanova JL, Bodemer C. Dupuis-Girod S, et al. Pediatrics. 2002 Jun;109(6):e97. doi: 10.1542/peds.109.6.e97. Pediatrics. 2002. PMID: 12042591 - Diagnosis and treatment in anhidrotic ectodermal dysplasia with immunodeficiency.
Kawai T, Nishikomori R, Heike T. Kawai T, et al. Allergol Int. 2012 Jun;61(2):207-17. doi: 10.2332/allergolint.12-RAI-0446. Allergol Int. 2012. PMID: 22635013 Review.
Cited by
- A comprehensive manually curated protein-protein interaction database for the Death Domain superfamily.
Kwon D, Yoon JH, Shin SY, Jang TH, Kim HG, So I, Jeon JH, Park HH. Kwon D, et al. Nucleic Acids Res. 2012 Jan;40(Database issue):D331-6. doi: 10.1093/nar/gkr1149. Epub 2011 Dec 1. Nucleic Acids Res. 2012. PMID: 22135292 Free PMC article. - Mechanistic insights into the activation of the IKK kinase complex by the Kaposi's sarcoma herpes virus oncoprotein vFLIP.
Bagnéris C, Senthil Kumar SL, Baratchian M, Britt HM, Assafa TE, Thalassinos K, Collins MK, Barrett TE. Bagnéris C, et al. J Biol Chem. 2022 Jun;298(6):102012. doi: 10.1016/j.jbc.2022.102012. Epub 2022 May 5. J Biol Chem. 2022. PMID: 35525271 Free PMC article. - Sclerosing bone dysplasias: leads toward novel osteoporosis treatments.
Fijalkowski I, Boudin E, Mortier G, Van Hul W. Fijalkowski I, et al. Curr Osteoporos Rep. 2014 Sep;12(3):243-51. doi: 10.1007/s11914-014-0220-5. Curr Osteoporos Rep. 2014. PMID: 24947952 Review. - Ectodermal Dysplasia - An Overview and Update.
Dev A, Malhi K, Mahajan R. Dev A, et al. Indian Dermatol Online J. 2024 Apr 23;15(3):405-414. doi: 10.4103/idoj.idoj_599_23. eCollection 2024 May-Jun. Indian Dermatol Online J. 2024. PMID: 38845644 Free PMC article. Review. - NF-kB overexpression and decreased immunoexpression of AR in the muscular layer is related to structural damages and apoptosis in cimetidine-treated rat vas deferens.
Koshimizu JY, Beltrame FL, de Pizzol JP Jr, Cerri PS, Caneguim BH, Sasso-Cerri E. Koshimizu JY, et al. Reprod Biol Endocrinol. 2013 Apr 9;11:29. doi: 10.1186/1477-7827-11-29. Reprod Biol Endocrinol. 2013. PMID: 23570504 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous