Biomaterial Database

The tax oncoprotein of human T-cell leukemia virus type 1 associates with and persistently activates IkappaB kinases containing IKKalpha and IKKbeta. 1998

Z L Chu, and J A DiDonato, and J Hawiger, and D W Ballard

Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.

The Tax oncoprotein of human T-cell leukemia virus type 1 (HTLV1) chronically activates transcription factor NF-kappaB by a mechanism involving degradation of IkappaBalpha, an NF-kappaB-associated cytoplasmic inhibitor. Tax-induced breakdown of IkappaBalpha requires phosphorylation of the inhibitor at Ser-32 and Ser-36, which is also a prerequisite for the transient activation of NF-kappaB in cytokine-treated T lymphocytes. However, it remained unclear how Tax interfaces with the cellular NF-kappaB/IkappaB signaling machinery to generate a chronic rather than a transient NF-kappaB response. We now demonstrate that Tax associates with cytokine-inducible IkappaB kinase (IKK) complexes containing catalytic subunits IKKalpha and IKKbeta, which mediate phosphorylation of IkappaBalpha at Ser-32 and Ser-36. Unlike their transiently activated counterparts in cytokine-treated cells, Tax-associated forms of IKK are constitutively active in either Tax transfectants or HTLV1-infected T lymphocytes. Moreover, point mutations in Tax that ablate its IKK-binding function also prevent Tax-mediated activation of IKK and NF-kappaB. Together, these findings suggest that the persistent activation of NF-kappaB in HTLV1-infected T-cells is mediated by a direct Tax/IKK coupling mechanism.

UI	MeSH Term	Description	Entries
D003593	Cytoplasm	The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)	Protoplasm,Cytoplasms,Protoplasms
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015368	Human T-lymphotropic virus 1	A strain of PRIMATE T-LYMPHOTROPIC VIRUS 1 isolated from mature T4 cells in patients with T-lymphoproliferation malignancies. It causes adult T-cell leukemia (LEUKEMIA-LYMPHOMA, T-CELL, ACUTE, HTLV-I-ASSOCIATED), T-cell lymphoma (LYMPHOMA, T-CELL), and is involved in mycosis fungoides, SEZARY SYNDROME and tropical spastic paraparesis (PARAPARESIS, TROPICAL SPASTIC).	ATLV,Adult T-Cell Leukemia-Lymphoma Virus I,HTLV-1,HTLV-I,Human T-Cell Leukemia Virus I,Leukemia Virus I, Human T-Cell,T-Cell Leukemia Virus I, Human,Adult T Cell Leukemia Lymphoma Virus I,Human T Cell Leukemia Virus I,Leukemia Lymphoma Virus I, Adult T Cell,Leukemia Virus I, Human T Cell,T Cell Leukemia Virus I, Human,Human T lymphotropic virus 1
D015490	HTLV-I Infections	Diseases caused by HUMAN T-LYMPHOTROPIC VIRUS 1.	Human T-lymphotropic Virus 1 Infection,Human T-lymphotropic Virus 1 Infections,Infections, HTLV-I,HTLV I Infections,HTLV-I Infection,Human T lymphotropic Virus 1 Infection,Human T lymphotropic Virus 1 Infections,Infection, HTLV-I,Infections, HTLV I
D016328	NF-kappa B	Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.	Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB
D016356	Gene Products, tax	Transcriptional trans-acting proteins of the promoter elements found in the long terminal repeats (LTR) of HUMAN T-LYMPHOTROPIC VIRUS 1 and HUMAN T-LYMPHOTROPIC VIRUS 2. The tax (trans-activator x; x is undefined) proteins act by binding to enhancer elements in the LTR.	Trans-Activator Protein p40(tax),Trans-Activator Protein p40(x),p40(tax),tax Gene Products,tax Protein,Gene Product, tax,Trans-Activator Protein p40(lor),Trans-Activator Protein p40x,Trans-Activator Protein pX,Transactivator Protein p40(x),Transactivator p40(tax),Transforming Antigen p40x,p40 tax,Antigen p40x, Transforming,Trans Activator Protein p40x,Trans Activator Protein pX,p40x, Trans-Activator Protein,p40x, Transforming Antigen,pX, Trans-Activator Protein,tax Gene Product
D017346	Protein Serine-Threonine Kinases	A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.	Protein-Serine-Threonine Kinases,Serine-Threonine Protein Kinase,Serine-Threonine Protein Kinases,Protein-Serine Kinase,Protein-Serine-Threonine Kinase,Protein-Threonine Kinase,Serine Kinase,Serine-Threonine Kinase,Serine-Threonine Kinases,Threonine Kinase,Kinase, Protein-Serine,Kinase, Protein-Serine-Threonine,Kinase, Protein-Threonine,Kinase, Serine-Threonine,Kinases, Protein Serine-Threonine,Kinases, Protein-Serine-Threonine,Kinases, Serine-Threonine,Protein Kinase, Serine-Threonine,Protein Kinases, Serine-Threonine,Protein Serine Kinase,Protein Serine Threonine Kinase,Protein Serine Threonine Kinases,Protein Threonine Kinase,Serine Threonine Kinase,Serine Threonine Kinases,Serine Threonine Protein Kinase,Serine Threonine Protein Kinases
D051550	I-kappa B Kinase	A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.	CHUK Kinase,Conserved Helix-Loop-Helix Ubiquitous Kinase,I Kappa B alpha-Associated Protein Kinase,I kappa B Kinase,IKBKB,IKK 1 Kinase,IKK 2 Kinase,IKK alpha,IKK beta,IKK epsilon,IKK gamma,IKKepsilon,IkappaB Kinase,IkappaB Kinase alpha,IkappaB Kinase beta,IkappaB Kinase epsilon,IkappaB Kinase gamma,IkappaBalpha Kinase,NF-kappaB Essential Modifier,NK-kappa B-Activating Kinase NAK,B Kinase, I-kappa,Conserved Helix Loop Helix Ubiquitous Kinase,Essential Modifier, NF-kappaB,I Kappa B alpha Associated Protein Kinase,Kinase alpha, IkappaB,Kinase beta, IkappaB,Kinase epsilon, IkappaB,Kinase, I-kappa B,Kinase, IkappaB,NF kappaB Essential Modifier,NK kappa B Activating Kinase NAK
D019169	Jurkat Cells	A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.	Cell, Jurkat,Cells, Jurkat,Jurkat Cell