Crystal Structure of Inhibitor of Growth 4 (ING4) Dimerization Domain Reveals Functional Organization of ING Family of Chromatin-binding Proteins

Culurgioni, Simone; Muñoz, Inés G.; Moreno, Alberto; Palacios, Alicia; Villate, Maider; Palmero, Ignacio; Montoya, Guillermo; Blanco, Francisco J.

doi:10.1074/jbc.m111.330001

Cited by 23 publications

(26 citation statements)

References 49 publications

(43 reference statements)

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“…ING4 associates with p53 via its NLS region, leading to enhanced acetylation of p53 on Lys-382 and transcriptional activity of p53 [24,27]. ING4 dimerization through its N-terminal region is essential for apoptosis and growth inhibition [28]. In this study, we found that the NLS domain was also necessary for the binding of ING4 to AUF1 and the suppression of MYC translation and cell proliferation in p53-null K562 cells.…”

Section: Discussionmentioning

confidence: 58%

ING4 inhibits the translation of proto‐oncogene MYC by interacting with AUF1

et al. 2013

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a b s t r a c tThe ING4 tumor suppressor plays a significant role in various cancer-related cellular processes. AUF1 affects the stability and/or translation of multiple mRNAs via binding to an AU-rich element in the 3 0 -untranslated regions. In this study, we identify AUF1 as a novel and direct binding partner of ING4. mRNP immunoprecipitation assays indicated that ING4, AUF1 and MYC mRNA present in the same mRNP complex. ING4 suppressed MYC protein expression without altering MYC mRNA levels, and abolished the cell proliferation induced by AUF1 in K562 cells. These results suggest that ING4 may regulate MYC translation by its association with AUF1. Structured summary of protein interactions:ING4binds to AUF1 p40 by pull down (View interaction) ING4physically interacts with AUF1 by anti tag coimmunoprecipitation (View Interaction: 1, 2) ING4binds to AUF1 p37 by pull down (View Interaction: 1, 2) ING4 binds to AUF1 p42 by pull down (View interaction) ING4binds to AUF1 p45 by pull down (View interaction) ING4physically interacts with AUF1 by anti bait coimmunoprecipitation (View Interaction: 1,2,3,4,5,6) ING4binds to AUF1 by pull down (View interaction)

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Section: Discussionmentioning

confidence: 58%

ING4 inhibits the translation of proto‐oncogene MYC by interacting with AUF1

et al. 2013

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“…dimer: in green, the N-terminal coiled-coil domain responsible for the antiparallel dimerization; in blue, the PHD domain responsible for binding to the histone H3 tail; and in magenta, the connecting region containing the NLS. Below the scheme are the crystal structures of a dimer of the N-terminal domain [9] (PDB ID: 4AFL) and the PHD finger [7] (PDB ID: 2VNF). The NLS region was randomly built to connect the two domains and the positions of lysine and arginine residues are indicated by red spheres.…”

Section: Cloningmentioning

confidence: 99%

“…This modification is recognized by its conserved C-terminal plant homeodomain (PHD) with micromolar affinity [5][6][7]. The N-terminal region of ING4 is folded into a coiled-coil domain, forming an antiparallel dimer in solution and in living cells [8,9]. Therefore, ING4 can be described as an elongated dimer with two PHD fingers pointing to opposite directions and tethered by a disordered central region approximately 85 residues long ( Fig.…”

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confidence: 99%

The tumor suppressor inhibitor of growth 4 binds double‐stranded DNA through its disordered central region

et al. 2016

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The tumor suppressor inhibitor of growth 4 (ING4) regulates chromatin structure by recruiting the histone acetyl transferase complex HBO1 to sites with histone H3 trimethylated at K4. ING4 dimerizes through its N-terminal domain and recognizes H3K4me3 by the C-terminal plant homeodomain (PHD). The central region of ING4 is disordered and contains the nuclear localization signal. Here, utilizing electrophoresis and nuclear magnetic resonance, we show that ING4 binds double-stranded DNA through its central region with micromolar affinity. Our findings suggest that the cooperativity arising from the presence of two DNA-binding regions in the ING4 dimer, as well as two H3K4me3-binding PHD fingers, may strengthen nucleosome binding and HBO1 complex recruitment.

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“…Some PHD protein specifically recognizes tri-and di-methylated H3K4 (H3K4me3/2), with H3K4me3 as the preferred binding partner [100]. Others recognize unmodified histone residues such as H3R2 [101]. The ING (Inhibitor of Growth) family is one of the wellstudied tumor suppressors with PHD finger at its C-terminal [102].…”

Section: The Importance Of Chromatin Remodelingmentioning

confidence: 99%

Chromatin Memory in the Development of Human Cancers

2014

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Cancer is a complex disease with acquired genomic and epigenomic alterations that affect cell proliferation, viability and invasiveness. Almost all the epigenetic mechanisms including cytosine methylation and hydroxymethylation, chromatin remodeling and non-coding RNAs have been found associate with carcinogenesis and cancer specific expression profile. Altered histone modification as an epigenetic hallmark is frequently found in tumors. Understanding the epigenetic alterations induced by carcinogens or infectious agents may help us understand early epigenetic changes prior to the development of cancer. In this review, we focus on chromatin remodeling and the associated histone modifiers in the development of cancer; the application of these modifiers as a cancer therapy target in different clinical trial phases is also discussed.

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Crystal Structure of Inhibitor of Growth 4 (ING4) Dimerization Domain Reveals Functional Organization of ING Family of Chromatin-binding Proteins

Cited by 23 publications

References 49 publications

ING4 inhibits the translation of proto‐oncogene MYC by interacting with AUF1

ING4 inhibits the translation of proto‐oncogene MYC by interacting with AUF1

The tumor suppressor inhibitor of growth 4 binds double‐stranded DNA through its disordered central region

Chromatin Memory in the Development of Human Cancers

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