The emerging role of the Ikaros stem cell factor in the neuroendocrine system

Ezzat, Shereen; Sylvia, L.

doi:10.1677/jme-08-0045

Cited by 19 publications

(8 citation statements)

References 35 publications

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“…Helios expression outside of the hematopoietic system is poorly characterized at present. Together with reports showing that Ikaros controls neural and endocrine functions (42)(43)(44), the severe viability defect of Helios Ϫ/Ϫ mice provides further evidence that Ikaros family members exert important functions beyond the hematopoietic system.…”

Section: Discussionsupporting

confidence: 55%

Helios Deficiency Has Minimal Impact on T Cell Development and Function

Cai

Dierich

Oulad‐Abdelghani

et al. 2009

The Journal of Immunology

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Helios is a member of the Ikaros family of zinc finger transcription factors. It is expressed mainly in T cells, where it associates with Ikaros-containing complexes and has been proposed to act as a rate-limiting factor for Ikaros function. Overexpression of wild-type or dominant-negative Helios isoforms profoundly alters αβ T cell differentiation and activation, and endogenous Helios is expressed at strikingly high levels in regulatory T cells. Helios has also been implicated as a tumor suppressor in human T cell acute lymphoblastic leukemias. These studies suggest a central role for Helios in T cell development and homeostasis, but whether this protein is physiologically required in T cells is unclear. We report herein that inactivation of the Helios gene by homologous recombination does not impair the differentiation and effector cell function of αβ and γδ T cells, NKT cells, and regulatory T cells. These results suggest that Helios is not essential for T cells, and that its function can be compensated for by other members of the Ikaros family.

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Section: Discussionsupporting

confidence: 55%

Helios Deficiency Has Minimal Impact on T Cell Development and Function

Cai

Dierich

Oulad‐Abdelghani

et al. 2009

The Journal of Immunology

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“…As a family, Ikaros is susceptible to methylation of CpG islands in one of its exons. Through an unknown mechanism, PAs specifically overexpress a dominant negative alternatively spliced form of Ikaros [52,66,69]. This spliced form subsequently upregulates an anti-apoptotic signal through altering gene accessibility.…”

Section: Resultsmentioning

confidence: 99%

The Role of Epigenetic Modification in Tumorigenesis and Progression of Pituitary Adenomas: A Systematic Review of the Literature

et al. 2013

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BackgroundPituitary adenomas (PAs) are commonly occurring neoplasms with diverse endocrine and neurological effects. Although somatic gene mutations are uncommon in sporadic PAs, recent studies lend support to epigenetic modification as a potential cause of tumorigenesis and tumor progression.MethodsA systematic literature review of the PubMed and Google Scholar databases was conducted to identify abstracts (n=1,082) pertaining to key targets and mechanisms implicated in epigenetic dysregulation of PAs published between 1993-2013. Data regarding histopathological subtype, target genes, mode of epigenetic modification, and clinical correlation were recorded and analyzed.ResultsOf the 47 that studies met inclusion criteria and focused on epigenomic assessment of PAs, only 2 were genome-scale analyses. Current evidence supports epigenetic alteration in at least 24 PA genes, which were categorized into four groups based on function and epigenetic alteration: 1) Sixteen tumor suppressor genes silenced via DNA methylation; 2) Two oncogenes overexpressed via histone acetylation and hypomethylation; 3) Three imprinted genes with selective allelic silencing; and 4) One epigenome writer inducing abnormal genome-scale activity and 5) Two transcription regulators indirectly modifying the genome. Of these, 5 genes (CDKN2A, GADD45y, FGFR2, caspase-8, and PTAG) showed particular susceptibility to epigenetic modification, with abnormal DNA methylation in >50% of PA samples. Several genes displayed correlations between epigenetic modification and clinically relevant parameters, including invasiveness (CDKN2A; DAPK; Rb1), sex (MAGE-A3), tumor size (GNAS1), and histopathological subtype (CDKN2A; MEG3; p27; RASSF1A; Rb1).ConclusionsEpigenetic modification of selected PA genes may play a key role in tumorigenesis and progression, which may translate into important diagnostic and therapeutic applications.

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“…The GC-induced cellular exportation of ANXA1 in the rodent anterior pituitary gland parallels the onset of the steroid inhibition of ACTH secretion, both emerging within 15 min and reaching a maximum within 2 h Synthesis FUnit: see figures 6 and 9(left) ACTH synthesis regulation: Regulation of the ACTH precursor gene (POMC) is mainly transcriptional. The Ikaros (Ik1), Tpit and Pitx1 proteins that are present in corticotroph cells, bind to the POMC promoter and upregulate its expresssion, they are needed for normal POMC transcription as well as for corticotroph differentiation and population growing [52,51]; Ik1 functions as a potentiator of transcription by remodeling the densely packaged chromatin environment of POMC, allowing activation by Tpit and coactivators [52]. Promoter elements are present in the POMC gene region that are responsive to stimulation by CRH and AVP [154].…”

Section: Membrane Depolarizationmentioning

confidence: 99%

A Hierarchical Model of the Hypothalamo-Adreno-Pituitary system

Rota

Vuza

Climescu-Haulica

2019

Preprint

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We present a model of the Hypothalamo-Adreno-Pituitary (HPA) system; our approach is hierarchical and biologically sound, reflecting the complexity of the real HPA system. The structure of the conceptual model is based on theoretical frameworks of biological complex systems and its implementation takes advantage of recent hybrid automata modelling and analysis tools, being modular and reflecting parameter and mechanisms uncertainties.

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The emerging role of the Ikaros stem cell factor in the neuroendocrine system

Cited by 19 publications

References 35 publications

Helios Deficiency Has Minimal Impact on T Cell Development and Function

Helios Deficiency Has Minimal Impact on T Cell Development and Function

The Role of Epigenetic Modification in Tumorigenesis and Progression of Pituitary Adenomas: A Systematic Review of the Literature

A Hierarchical Model of the Hypothalamo-Adreno-Pituitary system

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