Direct Protein Interactions Are Responsible for Ikaros-GATA and Ikaros-Cdk9 Cooperativeness in Hematopoietic Cells

Bottardi, Stefania; Mavoungou, Lionel; Bourgoin, Vincent; Mashtalir, Nazar; Affar, El Bachir; Milot, Éric

doi:10.1128/mcb.00296-13

Cited by 19 publications

(19 citation statements)

References 101 publications

(162 reference statements)

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“…The release of active PTEFb is also facilitated by the phosphorylation of HEXIM1, which associates with the 7SK snRNA repressive complex, through the PI3D/Akt or PKC kinase signaling pathways [72,73]. IKAROS interacts with CDK9 [7,25] and PP1 [7,74] and, interestingly, facilitates the recruitment of both CDK9 and PP1a to specific genes in hematopoietic cells [7]. The IKAROS-mediated transfer of PP1a to CDK9 promotes P-TEFb association with gene regulatory regions as well as P-TEFb activation [7] through dephosphorylation of CDK9 at Thr-186 and, possibly, Ser-175 [71].…”

Section: Ikaros and Control Of Transcription Elongationmentioning

confidence: 98%

“…During transcription initiation IKAROS can directly participate in PIC formation at target genes through interaction with the GTFs TFIIB and TBP [52]. In hematopoietic progenitors as well as in erythroid and lymphoid cells, IKAROS interacts with the hematopoietic GATA factors (GATA1, GATA2, and GATA3) [25,53]. GATA factors are zinc-finger proteins capable of promoting both transcription activation and repression [54].…”

Section: Ikaros and Control Of Transcription Initiationmentioning

confidence: 99%

“…The C-terminal zinc-finger domain, which is characterized by two C2H2 fingers (F5 and F6), is involved in IKAROS heterodimerization and -multimerization with various protein partners [7,[25][26][27][28]. Several IKAROS isoforms are produced by the differential splicing of exons three to eight [27,29,30].…”

Section: Ikaros Structure and Associated Diseasesmentioning

confidence: 99%

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IKAROS: a multifunctional regulator of the polymerase II transcription cycle

2015

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Section: Ikaros and Control Of Transcription Elongationmentioning

confidence: 98%

Section: Ikaros and Control Of Transcription Initiationmentioning

confidence: 99%

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IKAROS: a multifunctional regulator of the polymerase II transcription cycle

2015

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“…Direct interaction of IKZF1 with GATA proteins has been previously demonstrated. 41 Together, these data emphasize the similarity in gene expression between monosomy 7 and focal IKZF1-deleted pediatric AML patients. …”

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confidence: 91%

Recurrent deletions of IKZF1 in pediatric acute myeloid leukemia

et al. 2015

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© F e r r a t a S t o r t i F o u n d a t i o nby controlling transcriptional regulators, such as GATA1 and RUNX1. 18,20 Although IKZF1 is not required for the initial differentiation towards granulocytes and monocytes, IKZF1 represses differentiation of the basophilic granulocyte lineage and promotes early maturation and survival of the neutrophil granulocyte lineage. 17,21,22 In pediatric AML, monosomy 7 is found in only 4%-5% of patients. The 5-year OS and EFS of pediatric AML patients with monosomy 7 with or without additional cytogenetic or chromosomal aberrations are poor. 23 In adult AML, monosomy 7 is the most frequent single monosomy and has a similar poor 4-year OS as compared to other single autosomal monosomies. 24 Deletions of the short arm of chromosome 7, 7p (del7p) were recurrently found in adult de novo AML and secondary AML developed from myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN). [25][26][27] Furthermore, 7p deletions were mapped to the IKZF1 locus and it was shown that loss of IKZF1 is acquired during the progression of MPN to secondairy AML, indicating that loss of IKZF1 contributes to the transformation from MPN to AML. 25 Together, these studies demonstrate that IKZF1 may play a role in myeloid differentiation and that loss of IKZF1 may contribute to myeloid oncogenesis. We, therefore, hypothesized that, in pediatric AML patients with monosomy 7, IKZF1 may be an important player. In this study, we analyzed the frequency of IKZF1 deletions in a pediatric AML cohort, and studied the difference in gene expression of cases with focal IKZF1 deletions, and cases with monosomy 7. Methods Patients' samplesSamples were provided by the Dutch Childhood Oncology Group (DCOG, the Netherlands), the AML-Berliner-FrankfurtMünster Study Group (Germany and Czech Republic), the SaintLouis Hospital (France), and the Royal Hospital for Sick Children (UK). Isolation of genomic DNA and total cellular RNA was performed using Trizol reagent. Each study group provided morphological and cytogenetic classification and clinical data. Institutional review board approval for these studies had been obtained in the participating centers. Detection of deletions and mutations of IKZF1Multiplex ligation-dependent probe amplification (MLPA) was performed using the p335-B1;ALL-IKZF1 kit (MRC Holland, Amsterdam, the Netherlands; data available at http: //www.mlpa.com). The data were analyzed with GeneMarker v. 1.85 (SoftGenetics, State College, Pennsylvania, USA). Data were normalized to reference probes and control samples. A deletion was defined as a peak ratio below 0.75; an amplification was defined as a peak ratio above 1.25.Array comparative genomic hybridization (Array-CGH) was performed using the human genome CGH Microarray 105K (Agilent Technologies, Santa Clara, California, USA) according to the manufacturer's protocol; data were analyzed with Genomic Workbench v. 5.0.14 (Agilent Technologies, Santa Clara, California, USA).Direct sequencing was used to analyze mutations or frameshif...

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“…154 Recently it has been shown that Ikaros needs to interact with the GATA family of transcription factors and Cdk9 protein for appropriate chromatin binding and activation of its target genes. 155 Ikaros was shown to interact with GATA2 in hematopoietic progenitors, GATA1 in erythroid cells and GATA3 in lymphoid cells. One mechanism by the sustained GATA2 expression in the MPPs and/or CLP can prevent Ikaros GATA3 binding thereby preventing Ikaros mediated lymphoid priming.…”

Section: Gata2 Mediated Lymphoid Blockmentioning

confidence: 99%

Persistant GATA2 Expression Promotes Self-Renewal of Myeloid Progenitors and Blocks Lymphoid Differentiation.

Nandakumar¹

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Direct Protein Interactions Are Responsible for Ikaros-GATA and Ikaros-Cdk9 Cooperativeness in Hematopoietic Cells

Cited by 19 publications

References 101 publications

IKAROS: a multifunctional regulator of the polymerase II transcription cycle

IKAROS: a multifunctional regulator of the polymerase II transcription cycle

Recurrent deletions of IKZF1 in pediatric acute myeloid leukemia

Persistant GATA2 Expression Promotes Self-Renewal of Myeloid Progenitors and Blocks Lymphoid Differentiation.

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