Identification of 6-Furfuryladenine (Kinetin) in Human Urine

Barciszewski, Jan; Mielcarek, Michał; Stobiecki, Maciej; Siboska, Gunhild E.; Clark, Brian F. C.

doi:10.1006/bbrc.2000.3928

Cited by 52 publications

(41 citation statements)

References 23 publications

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“…The free base, kinetin, has been isolated in human urine at near similar concentrations (45). Moreover, kinetin is widely used in topical cosmetics (46)(47)(48) due to reports that it prevents morphological and nuclear changes associated with "cellular aging."…”

Section: Figurementioning

confidence: 99%

Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activity

Tiedemann¹,

Mao²,

Shi³

et al. 2008

J. Clin. Invest.

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Knockout and transgenic studies in mice demonstrate that normal somatic tissues redundantly express 3 cyclin D proteins, whereas tumor cells seem dependent on a single overexpressed cyclin D. Thus, selective suppression of the individual cyclin D deregulated in a tumor represents a biologically valid approach to targeted cancer therapy. In multiple myeloma, overexpression of 1 of the cyclin D proteins is a ubiquitous feature, unifying at least 7 different initiating genetic events. We demonstrate here that RNAi of genes encoding cyclin D1 and cyclin D2 (CCND1 and CCND2, respectively) inhibits proliferation and is progressively cytotoxic in human myeloma cells. By screening a chemical library using a cell-based assay for inhibition of CCND2 trans-activation, we identified the plant cytokinin kinetin riboside as an inhibitor of CCND2 trans-activation. Kinetin riboside induced marked suppression of CCND2 transcription and rapidly suppressed cyclin D1 and D2 protein expression in primary myeloma cells and tumor lines, causing cell-cycle arrest, tumor cell-selective apoptosis, and inhibition of myeloma growth in xenografted mice. Mechanistically, kinetin riboside upregulated expression of transcription repressor isoforms of cAMP-response element modulator (CREM) and blocked both trans-activation of CCND2 by various myeloma oncogenes and cis-activation of translocated CCND1, suggesting induction of an overriding repressor activity that blocks multiple oncogenic pathways targeting cyclin D genes. These data support targeted repression of cyclin D genes as a therapeutic strategy for human malignancies. IntroductionMultiple myeloma (MM) is a postgerminal center B cell malignancy characterized by clonal plasma cell expansion. The disease manifests clinically with anemia, monoclonal immunoglobulin, renal insufficiency, and lytic bone lesions and currently affects 63,000 people in the United States alone (1); moreover, as it is currently incurable, MM causes a disproportionate 2% of all cancer deaths.Although myeloma tumors present with complex karyotypes and an assortment of structural and numerical chromosomal abnormalities, these tumors are unified in their ubiquitous targeting of cyclin D genes for overexpression. Of MM tumors, 54% overexpress cyclin D1 (CCND1), 48% overexpress cyclin D2 (CCND2), 3% overexpress cyclin D3 (CCND3), and 8% overexpress both CCND1 and CCND2 (2). Deregulated expression of single CCND genes in MM occurs as the result of selective cyclin D gene trans-activation by deregulated transcription factors or from translocation of a single

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Section: Figurementioning

confidence: 99%

Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activity

Tiedemann¹,

Mao²,

Shi³

et al. 2008

J. Clin. Invest.

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“…Kinetin structure and properties have been already discussed in several reviews [1,[4][5][6][7]. In this paper, we would like to summarize the knowledge on kinetin and other cytokinins 50 years after their discovery.…”

Section: Introductionmentioning

confidence: 99%

Kinetin—A multiactive molecule

Barciszewski

Massino²,

Clark

2007

International Journal of Biological Macromolecules

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“…trans-zeatin, in a reaction catalyzed by enzymes from the group of cis -/trans -isomerases. The slow turnover rate of tRNA is, however, insufficient to fulfill the cell requirement for cytokinins (Barciszewski et al, 2000;Czerpak and Piotrowska, 2003;Haberer and Kieber, 2002). The key enzyme in the de novo synthesis pathway of cytokinin is adenosine phosphateisopentenyltransferase (IPT).…”

Section: Gibberellinsmentioning

confidence: 99%

New insights into the signaling and function of cytokinins in higher plants

Ciesielska¹,

Ruszkowski²,

Kasperska³

et al. 2012

bta

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Phytohormones (plant hormones) play a role in the regulation of cellular activities including cell division, elongation and differentiation, pattern formation, organogenesis, reproduction, sex determination, and responses to abiotic and biotic stress. The phytohormonal signal transduction pathways operate via cytokinin perception by transmembrane receptors consisting of two domains: an extracellular domain responsible for hormone binding and an intracellular domain, sensory His / Asp kinase (HK). Upon phytohormone binding, the receptor undergoes a conformational change which activates its protein kinase activity. The phosphorylated intracellular domain transfers the phosphoryl group to the His residue of the histidine phosphotransfer protein (HPt) which in turn phosphorylates Asp residue in the Response Regulator (RR). The phosphorylated RR protein acts as either a positive or negative transcription factor that interacts with the gene promoter or other target protein. The two-component signaling pathway, operating through the His-Asp phosphorelay, controls many physiological and developmental processes throughout the plant lifecycle (from seed-to-seed). Downstream plant hormone signaling also includes proteolysis of transcriptional regulators that block the activity of transcription factors. Two-component signaling operates more frequently in higher plants. Five classic plant hormones had been discovered by the middle of the twentieth century: auxins, cytokinins, gibberellins, ethylene and abscisic acid. The more recently characterized hormones include brassinosteroids, strigolactones, jasmonates and salicylates. Considering the tremendous work that has been undertaken during the last decades, in this review we decided to concentrate on cytokinin signaling in various plant developmental processes, including responses to biotic and abiotic stresses.

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Identification of 6-Furfuryladenine (Kinetin) in Human Urine

Cited by 52 publications

References 23 publications

Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activity

Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activity

Kinetin—A multiactive molecule

New insights into the signaling and function of cytokinins in higher plants

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