Publication Date:
1999-04-09
Description:
The gene encoding inhibitor of kappa B (IkappaB) kinase alpha (IKKalpha; also called IKK1) was disrupted by gene targeting. IKKalpha-deficient mice died perinatally. In IKKalpha-deficient fetuses, limb outgrowth was severely impaired despite unaffected skeletal development. The epidermal cells in IKKalpha-deficient fetuses were highly proliferative with dysregulated epidermal differentiation. In the basal layer, degradation of IkappaB and nuclear localization of nuclear factor kappa B (NF-kappaB) were not observed. Thus, IKKalpha is essential for NF-kappaB activation in the limb and skin during embryogenesis. In contrast, there was no impairment of NF-kappaB activation induced by either interleukin-1 or tumor necrosis factor-alpha in IKKalpha-deficient embryonic fibroblasts and thymocytes, indicating that IKKalpha is not essential for cytokine-induced activation of NF-kappaB.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takeda, K -- Takeuchi, O -- Tsujimura, T -- Itami, S -- Adachi, O -- Kawai, T -- Sanjo, H -- Yoshikawa, K -- Terada, N -- Akira, S -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):313-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Department of Pathology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10195895" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Differentiation
;
Cytoplasm/metabolism
;
DNA-Binding Proteins/metabolism
;
Epidermis/cytology/*embryology/metabolism
;
Extremities/*embryology/growth & development
;
Gene Expression Regulation, Developmental
;
Gene Targeting
;
I-kappa B Kinase
;
I-kappa B Proteins
;
Interleukin-1/pharmacology
;
Keratinocytes/cytology/metabolism
;
Limb Buds/enzymology
;
Limb Deformities, Congenital/*enzymology/genetics
;
Mice
;
*Myogenic Regulatory Factors
;
NF-kappa B/metabolism
;
Nuclear Proteins/genetics
;
Phosphorylation
;
Protein-Serine-Threonine Kinases/deficiency/genetics/*metabolism
;
Skin Abnormalities/*enzymology/genetics
;
Transcription Factor RelA
;
Tumor Necrosis Factor-alpha/pharmacology
;
Twist Transcription Factor
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
