“Functional mapping of the promoter region of the GNB2L1 human gene coding for RACK1 scaffold protein”

Vecchio, Igor Del; Zuccotti, Annalisa; Pisano, Federica; Canneva, Fabio; Lenzken, Silvia C.; Rousset, F; Corsini, Emanuela; Govoni, Stefano; Racchi, Marco

doi:10.1016/j.gene.2008.10.005

Cited by 29 publications

(49 citation statements)

References 44 publications

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“…Human RACK1 is encoded by the gene, GNB2L1 [guanine nucleotide binding protein (G-protein), beta polypeptide 2-like 1], which has 8 exons and 7 introns [63,64]. The open reading frame of the gene is 1142 bp and it encodes for a protein with 317 amino acids, registering as a 36 kDa protein on an SDS PAGE gel.…”

Section: Rack1 Gene and Structurementioning

confidence: 99%

“…Indeed, sequence alignments of RACK1 species from diverse organisms -- Tetrahymena thermophila, Saccharomyces cerevisiae, Arabidopsis thaliana and Drosophila melanogaster -- reveals a 43-76% sequence identity (Figure 6). GNB2L1 is mapped to chromosome 5q35.3, in close proximity to the telomere of chromosome 5 [63]. At least 6 other genes have been mapped to this region and it is a reported location for cytogenetic and molecular abnormalities [65-68].…”

Section: Rack1 Gene and Structurementioning

confidence: 99%

“…At least 6 other genes have been mapped to this region and it is a reported location for cytogenetic and molecular abnormalities [65-68]. The promoter region of GNB2L1 , which was found to have two alternative start sites of transcription, has binding sites for cardiac/smooth muscle specific c-Rel (NF-κB) [63,69]. RACK1 is highly expressed in most tissues [70], including the brain [71].…”

Section: Rack1 Gene and Structurementioning

confidence: 99%

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RACK1, A multifaceted scaffolding protein: Structure and function

Adams¹,

2011

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The Receptor for Activated C Kinase 1 (RACK1) is a member of the tryptophan-aspartate repeat (WD-repeat) family of proteins and shares significant homology to the β subunit of G-proteins (Gβ). RACK1 adopts a seven-bladed β-propeller structure which facilitates protein binding. RACK1 has a significant role to play in shuttling proteins around the cell, anchoring proteins at particular locations and in stabilising protein activity. It interacts with the ribosomal machinery, with several cell surface receptors and with proteins in the nucleus. As a result, RACK1 is a key mediator of various pathways and contributes to numerous aspects of cellular function. Here, we discuss RACK1 gene and structure and its role in specific signaling pathways, and address how posttranslational modifications facilitate subcellular location and translocation of RACK1. This review condenses several recent studies suggesting a role for RACK1 in physiological processes such as development, cell migration, central nervous system (CN) function and circadian rhythm as well as reviewing the role of RACK1 in disease.

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Section: Rack1 Gene and Structurementioning

confidence: 99%

Section: Rack1 Gene and Structurementioning

confidence: 99%

Section: Rack1 Gene and Structurementioning

confidence: 99%

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RACK1, A multifaceted scaffolding protein: Structure and function

Adams¹,

2011

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“…PKC activation enhances tyrosine phosphorylation of RACK1 (10), and this posttranslation modification might enable RACK1 to interact with other signaling proteins. The G-proteins β 1 and β 2 also share similar WD-repeats with RACK1, interact with the NH 2 -terminal region of the GR, and similarly comigrate into the nucleus and suppress the transcriptional activity of the GR in a dose-dependent manner (14, 33). …”

Section: Discussionmentioning

confidence: 99%

Interaction of the Mineralocorticoid Receptor With RACK1 and Its Role in Aldosterone Signaling

et al. 2017

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The mineralocorticoid receptor (MR) is a member of the steroid-thyroid hormone receptor superfamily of ligand-dependent transcription factors with diverse functions including the biological actions of aldosterone. Identification of the various transcriptional coregulators of MR is essential for understanding the complexity of MR signaling pathways under physiological and pathological conditions. We used a yeast two-hybrid system to find proteins that interact with a full-length MR and found, among other proteins, that MR interacted specifically with receptor for activated C kinase 1 (RACK1), a scaffolding protein. Overexpression of RACK1 using a tetracycline-inducible lentivirus in mouse cortical collecting duct M1 cells stably expressing the rat MR and a Gaussia luciferase gene reporter under a hormone-response element promoter resulted in enhanced agonist-dependent MR transactivation. Knockdown of RACK1 protein expression by short hairpin RNAs led to a significant reduction in MR activation of the reporter gene and the endogenous genes Ctla2α and Psca. We also demonstrated that RACK1 regulation of MR action is mediated through phosphorylation by the PKC-β signaling pathway. MR and RACK1 were coimmunoprecipitated using an MR antibody in male Sprague-Dawley brain tissue and M1-rMR cells, and colocalization in M1-rMR cells and male rat brains was confirmed by immunofluorescence and immunohistochemistry. The scaffolding protein RACK1 is associated with MR under basal and agonist-stimulated conditions and facilitates agonist-stimulated MR actions through PKC-β. These findings indicate that RACK1 is a newly described coactivator of MR.

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“…The increase of a 5 and RACK1 expression in leukemic progenitors from female patients could be secondary to the inflammatory niche and nuclear factor-kB activation (Del Vecchio et al, 2009;Sampaio et al, 2010). Sex differences in immune responses have been described.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in the GSK3β-mediated survival of adherent leukemic progenitors

et al. 2011

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Therapeutic resistance of acute myeloid leukemia stem cells, enriched in the CD34 þ 38 À 123 þ progenitor population, is supported by extrinsic factors such as the bone marrow niche. Here, we report that when adherent onto fibronectin or osteoblast components, CD34 þ 38 À 123 þ progenitors survive through an integrin-dependent activation of glycogen synthase kinase 3b (GSK3b) by serine 9-dephosphorylation. Strikingly, GSK3b-mediated survival was restricted to leukemic progenitors from female patients. GSK3b inhibition restored sensitivity to etoposide, and impaired the clonogenic capacities of adherent leukemic progenitors from female patients. In leukemic progenitors from female but not male patients, the scaffolding protein RACK1, activated downstream of a 5 b 1 -integrin engagement, was specifically upregulated and controlled GSK3b activation through the phosphatase protein phosphatase 2A (PP2A). In a mirrored manner, survival of adherent progenitors (CD34 þ 38 À ) from male but not female healthy donors was partially dependent on this pathway. We conclude that the GSK3b-dependent survival pathway might be sex-specific in normal immature population and flip-flopped upon leukemogenesis. Taken together, our results strengthen GSK3b as a promising target for leukemic stem cell therapy and reveal gender differences as a new parameter in anti-leukemia therapy.

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“Functional mapping of the promoter region of the GNB2L1 human gene coding for RACK1 scaffold protein”

Cited by 29 publications

References 44 publications

RACK1, A multifaceted scaffolding protein: Structure and function

RACK1, A multifaceted scaffolding protein: Structure and function

Interaction of the Mineralocorticoid Receptor With RACK1 and Its Role in Aldosterone Signaling

Sex differences in the GSK3β-mediated survival of adherent leukemic progenitors

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