Human T-Cell Leukemia Virus Oncoprotein Tax Represses Nuclear Receptor–Dependent Transcription by Targeting Coactivator TAX1BP1

Chin, King-Tung; Chun, Abel C.S.; Ching, Yick–Pang; Jeang, Kuan‐Teh; Jin, Dong-Yan

doi:10.1158/0008-5472.can-06-3053

Cited by 30 publications

(28 citation statements)

References 52 publications

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“…The N-terminal 1 to 420 residues encompass the first two coiled-coil structures, which contain an activation domain and a self-association domain. The C-terminal 421 to 789 residues encompass the third coiled-coil structure and two zinc finger domains (4,28). Based on this structural prediction, N-terminal (TXBP-Nter) and C-terminal (TXBP-Cter) truncation protein expression constructs were made ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Tax1BP1 is highly conserved across the species, with human Tax1BP1 sharing 79% and 81% identity with rat and mouse orthologs, respectively. It is a nuclear protein and is abundantly expressed in most human tissues and established cell lines (4,6).…”

mentioning

confidence: 99%

“…Tax1BP1 knockout mice exhibit elevated NF-B activation in response to tumor necrosis factor alpha and interleukin 1 stimulation. In addition, Tax1BP1 also serves as a transcriptional coactivator of glucocorticoid receptor by stimulating glucocorticoid response element-dependent reporter through its N-terminal activation domain (4).…”

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confidence: 99%

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Tax1BP1 Interacts with Papillomavirus E2 and Regulates E2-Dependent Transcription and Stability

Wang

Naidu

Sverdrup

et al. 2009

J Virol

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The papillomavirus E2 proteins regulate viral replication, gene transcription, and genome maintenance by interacting with other viral and host proteins. From a yeast two-hybrid screen, we identified the cellular protein Tax1BP1 as a novel binding partner of human papillomavirus type 18 (HPV18) E2. Tax1BP1 also interacts with the HPV16 and bovine papillomavirus type 1 (BPV1) E2 proteins, with the C-terminal region of Tax1BP1 interacting with the N-terminal transactivation domain of BPV1 E2. Tax1BP1 complexes with p300 and acts synergistically as a coactivator with p300 to enhance E2-dependent transcription. Using chromatin immunoprecipitation assays, we show that Tax1BP1 and E2 localize to the long control region on the BPV1 genome. Tax1BP1 was recently reported to bind ubiquitin and to function as an essential component of an A20 ubiquitin-editing complex. We demonstrate that Tax1BP1 plays a role in the regulation of the steady-state level of E2 by preventing its proteasomal degradation. These studies provide new insights into the regulation of E2 functions.The papillomavirus E2 protein is a key regulator of viral DNA replication, gene expression, and genome maintenance. The E2 proteins are structurally and functionally conserved across different papillomaviruses and are composed of an N-terminal transactivation domain (TAD) and a C-terminal dimerization and DNA binding domain (DBD) separated by a less conserved proline-rich hinge region (reviewed in reference 32). The N-terminal TAD is essential for E2 functions and interacts with numerous viral and cellular proteins, including the viral E1 protein, TFIIB, GPS2/AMF-1, MKlp2, CHlR1, Brd4, Brahma, NAP-1, p300/CBP, and p/CAF (20,23,24,29,33,36,38,44,45). The E2 DBD binds to the E2-responsive elements, specific palindromic sequences (ACCN 6 GGT) located mainly in the long control region (LCR) of the viral genome (1). Upon binding to the E2-responsive element, E2 activates gene transcription from viral early and late promoters. Besides the 410-amino-acid (aa) transcriptional activator E2, the open reading frame of the bovine papillomavirus type 1 (BPV1) E2 also encodes a transcriptional repressor, E2R (aa 162 to 410), which is expressed from the C-terminal part of the E2 open reading frame and represses E2-dependent transcription due to a lack of functional TAD (21).Tax1-binding protein 1 (Tax1BP1) (also named TXBP151 and T6BP) was originally identified as a binding partner of the human T-cell leukemia virus type 1 Tax oncoprotein (6, 28). The N-terminal region (aa 1 to 150) of Tax1BP1 contains a SKIP carboxyl homology (SKICH) domain. The central region (aa 150 to 600) is predicted to form three coiled-coil domains and is involved in self-dimerization. The C-terminal region (aa 601 to 789) encodes two zinc fingers. Tax1BP1 is highly conserved across the species, with human Tax1BP1 sharing 79% and 81% identity with rat and mouse orthologs, respectively. It is a nuclear protein and is abundantly expressed in most human tissues and established cell lines (4, 6).Tax1BP1...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Tax1BP1 Interacts with Papillomavirus E2 and Regulates E2-Dependent Transcription and Stability

Wang

Naidu

Sverdrup

et al. 2009

J Virol

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“…Fluorescence Resonance Energy Transfer (FRET) ImagingMulticolor fluorescence microscopy was performed as described previously (29,30). HeLa cells were transfected with pcDNA-CFP-TRBP, pcDNA-YFP-PACT, or both.…”

Section: Protein Purification and Protein Analysis-gst-trbpmentioning

confidence: 99%

Human TRBP and PACT Directly Interact with Each Other and Associate with Dicer to Facilitate the Production of Small Interfering RNA

Kok

Ching

et al. 2007

Journal of Biological Chemistry

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214

219

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Mammalian Dicer interacts with double-stranded RNA-binding protein TRBP or PACT to mediate RNA interference and micro-RNA processing. TRBP and PACT are structurally related but exert opposite regulatory activities on PKR. It is not understood whether TRBP and PACT are simultaneously required for Dicer. Here we show that TRBP directly interacts with PACT in vitro and in mammalian cells. TRBP and PACT form a triple complex with Dicer and facilitate the production of small interfering RNA (siRNA) by Dicer. Knockdown of both TRBP and PACT in cultured cells leads to significant inhibition of gene silencing mediated by short hairpin RNA but not by siRNA, suggesting that TRBP and PACT function primarily at the step of siRNA production. Taken together, these findings indicate that human TRBP and PACT directly interact with each other and associate with Dicer to stimulate the cleavage of double-stranded or short hairpin RNA to siRNA. Our work significantly alters the current model for the assembly and function of the Dicer-containing complex that generates siRNA and micro-RNA in human. RNA interference (RNAi)2 is an evolutionarily conserved mechanism for gene silencing mediated through small RNAs of ϳ22 nucleotides in length (1). At least two classes of small RNAs have been described in mammals, micro-RNAs (miRNA) produced from hairpin precursors and small interfering RNAs (siRNAs) derived from long double-stranded RNAs (dsRNAs) (2). Both miRNAs and siRNAs are generated by RNase III-type nuclease Dicer, and they are assembled into effector complex termed RNA-induced silencing complex (RISC) (3, 4). Although two Dicer enzymes Dcr1 and Dcr2 have been found in fruit flies and are responsible for the generation of miRNAs and siRNAs, respectively, there exists only one single Dicer in humans, which produces both miRNAs and siRNAs (3). Dcr2 is known to associate with a dsRNA-binding protein (dsRBP) termed R2D2, which binds to siRNA and facilitates its passage from Dcr2 to RISC (5, 6).A new family of dsRBPs, which includes Loquacious in Drosophila as well as TRBP and PACT in humans, has been shown recently to interact with Dicer and be required for its function in RNAi (7-12). Unlike its counterparts in Drosophila that have only one dsRBP partner, human Dicer appears to associate with two closely related dsRBPs, TRBP and PACT (10 -12). TRBP was originally identified and characterized by its high affinity for TAR, a hairpin RNA encoded by human immunodeficiency virus type 1 (13). PACT was initially cloned as a cellular protein activator of PKR kinase (14, 15). Although both PACT and TRBP bind to PKR and have three similar dsRNA-binding domains (dsRBDs), TRBP exerts an inhibitory effect on PKR (16 -20).Although both TRBP and PACT interact with and support the function of human Dicer in RNAi (10 -12), it is not understood whether their binding with Dicer is simultaneous or mutually exclusive. TRBP and PACT are closely related, and both are capable of homodimerization (21,22). In addition, they share two binding partners, [16][17][...

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“…Blots were blocked with 5% skimmed milk, followed by incubation with primary antibodies. Blots were then incubated with goat anti-rabbit or anti-mouse secondary antibody conjugated to horseradish peroxidase (Amersham) and visualized by enhanced chemiluminescence (Amersham) as described previously (Chin et al, 2007a;Chin et al, 2007b;Siu et al, 2008).…”

Section: Western Blottingmentioning

confidence: 99%

N-linked glycosylation is required for optimal proteolytic activation of membrane-bound transcription factor CREB-H

Chan

Mak

Chin

et al. 2010

Journal of Cell Science

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SummaryCREB-H is a liver-enriched bZIP transcription factor of the CREB3 subfamily. CREB-H is activated by intramembrane proteolysis that removes a C-terminal transmembrane domain. Aberrant expression of CREB-H is implicated in liver cancer. In this study we characterized N-linked glycosylation of CREB-H in the luminal domain at the C-terminus. We found that CREB-H is modified at three N-linked glycosylation sites in this region. Disruption of all three sites by site-directed mutagenesis completely abrogated N-linked glycosylation of CREB-H. The unglycosylated mutant of CREB-H was not unstable, unfolded or aggregated. Upon stimulation with an activator of intramembrane proteolysis such as brefeldin A and KDEL-tailed site 1 protease, unglycosylated or deglycosylated CREB-H was largely uncleaved, retained in an inactive form in the endoplasmic reticulum, and less capable of activating transcription driven by unfolded protein response element or C-reactive protein promoter. Taken together, our findings suggest that N-linked glycosylation is required for full activation of CREB-H through intramembrane proteolysis. Our work also reveals a novel mechanism for the regulation of CREB-H-dependent transcription.

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Human T-Cell Leukemia Virus Oncoprotein Tax Represses Nuclear Receptor–Dependent Transcription by Targeting Coactivator TAX1BP1

Cited by 30 publications

References 52 publications

Tax1BP1 Interacts with Papillomavirus E2 and Regulates E2-Dependent Transcription and Stability

Tax1BP1 Interacts with Papillomavirus E2 and Regulates E2-Dependent Transcription and Stability

Human TRBP and PACT Directly Interact with Each Other and Associate with Dicer to Facilitate the Production of Small Interfering RNA

N-linked glycosylation is required for optimal proteolytic activation of membrane-bound transcription factor CREB-H

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