Dissection of functional NF-Y-RFX cooperative interactions on the MHC class II Ea promoter

Caretti, Giuseppina; Cocchiarella, Fabienne; Sidoli, Cristina; Villard, Jean; Peretti, Marie; Reith, Walter; Mantovani, Roberto

doi:10.1006/jmbi.2000.4028

Cited by 36 publications

(32 citation statements)

References 49 publications

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“…80 Co-transfections of the NF-Y trimer with TFs binding the loci neighboring CCAAT boxes in mammalian and Drosophila cells synergistically activate transcription of CCAAT promoters. 52,81,82 Finally, transfections of recombinant proteins in which NF-YA was linked to a cell-penetrating TAT peptide activate endogenous CCAAT genes but not CCAAT-less units. 83,84 All these features are quite standard for TFs: sequence specificity, modularity of DBD and TA, and synergistic activation with neighboring TFs.…”

Section: Nf-y Is the Sequence-specific Ccaat Factormentioning

confidence: 99%

Targeting the Y/CCAAT box in cancer: YB-1 (YBX1) or NF-Y?

Dolfini

Mantovani

2013

Cell Death Differ

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The Y box is an important sequence motif found in promoters and enhancers containing a CCAAT box -one of the few elements enriched in promoters of large sets of genes overexpressed in cancer. The search for the transcription factor(s) acting on it led to the biochemical purification of the nuclear factor Y (NF-Y) heterotrimer, and to the cloning -through the screening of expression libraries -of Y box-binding protein 1 (YB-1), an oncogene, overexpressed in aggressive tumors and associated with drug resistance. These two factors have been associated with Y/CCAAT-dependent activation of numerous growth-related genes, notably multidrug resistance protein 1. We review two decades of data indicating that NF-Y ultimately acts on Y/CCAAT in cancer cells, a notion recently confirmed by genome-wide data. Other features of YB-1, such as post-transcriptional control of mRNA biology, render it important in cancer biology.

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Section: Nf-y Is the Sequence-specific Ccaat Factormentioning

confidence: 99%

Targeting the Y/CCAAT box in cancer: YB-1 (YBX1) or NF-Y?

Dolfini

Mantovani

2013

Cell Death Differ

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“…NF-Y is an ubiquitous transcription factor composed of the NF-YA, NF-YB, and NF-YC subunits that interact in vivo and then bind a consensus DNA sequence present in the Y box of the MHC-II promoters (57,58). NF-Y interacts with CIITA, contributing to the formation of the enhanceosome on the promoter-enhancer region of all MHC-II genes, allowing their regulated transcription (45)(46)(47)(48)(49)(50). It has been shown that NF-YB directly binds to Tax-1 (59).…”

Section: The Cellular Transcription Factor Nf-y Inhibits the Tax-2-dementioning

confidence: 99%

“…MHC-II-encoded molecules present peptides to the antigen receptor of CD4 ϩ T cells, whose activation is required to trigger and modulate both humoral and cellular immune responses (44). CIITA is a non-DNA-binding transcriptional integrator recruited to MHC-II promoters via multiple interactions with transcription factors bound to DNA, including the regulatory factor X and the nuclear factor Y (NF-Y) complexes (45)(46)(47)(48)(49)(50).…”

mentioning

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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“…The complex architecture of proteins that are directly or indirectly bound to MHC II promoters is achieved by multiple protein-protein interactions within the RFX and NFY complexes, between these complexes, and with CIITA, the master switch that triggers the transcription of MHC II genes (8,11,14,33). The RFX complex is composed of three subunits, namely, RFX5, RFXAP, and RFXANK(B).…”

mentioning

confidence: 99%

Analysis of Ankyrin Repeats Reveals How a Single Point Mutation in RFXANK Results in Bare Lymphocyte Syndrome

Nekrep

Geyer

Jabrane‐Ferrat

et al. 2001

Molecular and Cellular Biology

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Ankyrin repeats are well-known structural modules that mediate interactions between a wide spectrum of proteins. The regulatory factor X with ankyrin repeats (RFXANK) is a subunit of a tripartite RFX complex that assembles on promoters of major histocompatibility complex class II (MHC II) genes. Although it is known that RFXANK plays a central role in the nucleation of RFX, it was not clear how its ankyrin repeats mediate the interactions within the complex and with other proteins. To answer this question, we modeled the RFXANK protein and determined the variable residues of the ankyrin repeats that should contact other proteins. Site-directed alanine mutagenesis of these residues together with in vitro and in vivo binding studies elucidated how RFXAP and CIITA, which simultaneously interact with RFXANK in vivo, bind to two opposite faces of its ankyrin repeats. Moreover, the binding of RFXAP requires two separate surfaces on RFXANK. One of them, which is located in the ankyrin groove, is severely affected in the FZA patient with the bare lymphocyte syndrome. This genetic disease blocks the expression of MHC II molecules on the surface of B cells. By pinpointing the interacting residues of the ankyrin repeats of RFXANK, the mechanism of this subtype of severe combined immunodeficiency was revealed.

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Dissection of functional NF-Y-RFX cooperative interactions on the MHC class II Ea promoter

Cited by 36 publications

References 49 publications

Targeting the Y/CCAAT box in cancer: YB-1 (YBX1) or NF-Y?

Targeting the Y/CCAAT box in cancer: YB-1 (YBX1) or NF-Y?

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

Analysis of Ankyrin Repeats Reveals How a Single Point Mutation in RFXANK Results in Bare Lymphocyte Syndrome

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