GTP Binding by Class II Transactivator: Role in Nuclear Import

Harton, Jonathan A.; Cressman, Drew E.; Chin, Keh Chuang; Der, Channing J.; Ting, Jenny P.‐Y.

doi:10.1126/science.285.5432.1402

Cited by 90 publications

(111 citation statements)

References 44 publications

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“…This dual subcellular distribution is the net result of multiple nuclear import and nuclear export signals (53,(60)(61)(62)(63)(64)(65). Because Tax-2 activates the viral promoter in the nucleus, it is likely that CIITA inhibits Tax-2 at the nuclear level.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y

Tosi

Pilotti

Mortara

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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The master regulator of MHC-II gene transcription, class II transactivator (CIITA), acts as a potent inhibitor of human T cell leukemia virus type 2 (HTLV-2) replication by blocking the activity of the viral Tax-2 transactivator. Here, we show that this inhibitory effect takes place at the nuclear level and maps to the N-terminal 1-321 region of CIITA, where we identified a minimal domain, from positions 64 -144, that is strictly required to suppress Tax-2 function. Furthermore, we show that Tax-2 specifically cooperates with cAMP response element binding protein-binding protein (CBP) and p300, but not with p300͞CBP-associated factor, to enhance transcription from the viral promoter. This finding represents a unique difference with respect to Tax-1, which uses all three coactivators to transactivate the human T cell leukemia virus type 1 LTR. Direct sequestering of CBP or p300 is not the primary mechanism by which CIITA causes suppression of Tax-2. Interestingly, we found that the transcription factor nuclear factor Y, which interacts with CIITA to increase transcription of MHC-II genes, exerts a negative regulatory action on the Tax-2-mediated HTLV-2 LTR transactivation. Thus, CIITA may inhibit Tax-2 function, at least in part, through nuclear factor Y. These findings demonstrate the dual defensive role of CIITA against pathogens: it increases the antigen-presenting function for viral determinants and suppresses HTLV-2 replication in infected cells. Tax-2 MHC class II ͉ viral replication ͉

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Section: Discussionmentioning

confidence: 99%

Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y

Tosi

Pilotti

Mortara

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…CIITA has been shown to interact with several other transcriptional activators, including TAFII32, Bob-1, RFX5, RFXANK, CREB, CREB binding protein, PTEFb, and NF-YB and C (34, 38 -42, 58, 59). CIITA also is unique in that it is the only transcriptional activator known to be regulated by GTP binding (43). Though the DN␣ and DO␤ gene promoters also contain W, X, and Y boxes, expression of these genes is often incongruous with other MHC class II-associated genes (12,15,44), and whether DN␣ and DO␤ are induced by RFX or CIITA remains an open question.…”

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confidence: 99%

Identification of Class II Transcriptional Activator-Induced Genes by Representational Difference Analysis: Discoordinate Regulation of the DNα/DOβ Heterodimer

Taxman

Cressman

Ting

2000

The Journal of Immunology

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Class II transcriptional activator (CIITA) is a master regulator of MHC class II genes, including DR, DP, and DQ, and MHC class II-associated genes DM and invariant chain. To determine the repertoire of genes that is regulated by CIITA and to identify uncharacterized CIITA-inducible genes, we used representational difference analysis. Representational difference analysis screens for differentially expressed transcripts. All CIITA-induced genes were MHC class II related. We have identified the α subunit, DNα, of the class II processing factor DO as an additional CIITA-inducible gene. Northern analysis confirmed that DNα is induced by IFN-γ in 2fTGH fibrosarcoma cells, and CIITA is necessary for high-level expression in B cells. The β subunit, DOβ, is not inducible in fibrosarcoma cells by IFN-γ or exogenous CIITA expression. Moreover, in contrast to other class II genes, DOβ expression remains high in the absence of CIITA in B cells. The promoters for DNα and DOβ contain the highly conserved WXY motifs, and, like other class II genes, expression of both DNα and DOβ requires RFX. These findings demonstrate that both DNα and DOβ are regulated by RFX. However, DNα is defined for the first time as a CIITA-inducible gene, and DOβ as a MHC class II gene whose expression is independent of CIITA.

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“…The question of which kinase or combinations of kinases might phosphorylate CIITA to enhance its activity is still unanswered. CIITA also has a GTP binding domain with homology to the RAS superfamily that is important for self-association, nuclear localization, and activation of MHC-II (17,(22)(23)(24). In addition, there is a leucine-rich repeat (LRR) at the C terminus that is necessary for self-assembly, nuclear import, and dominant-negative function for MHC-II (25)(26)(27).…”

mentioning

confidence: 99%

Major Histocompatibility Class II Transactivator (CIITA) Mediates Repression of Collagen (COL1A2) Transcription by Interferon γ (IFN-γ)

Wang

Butticè

et al. 2004

Journal of Biological Chemistry

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GTP Binding by Class II Transactivator: Role in Nuclear Import

Cited by 90 publications

References 44 publications

Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y

Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y

Identification of Class II Transcriptional Activator-Induced Genes by Representational Difference Analysis: Discoordinate Regulation of the DNα/DOβ Heterodimer

Major Histocompatibility Class II Transactivator (CIITA) Mediates Repression of Collagen (COL1A2) Transcription by Interferon γ (IFN-γ)

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