AMY-1 is a trigger for the erythrocyte differentiation of K562 cells.

Furusawa, Mitsuhiro; Onishi, Toshio; Taira, Takahiro; Iguchi-Ariga, S. M. M.; Ariga, Hiroyoshi

doi:10.3892/ijo.16.2.339

Cited by 12 publications

(16 citation statements)

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“…In silico analysis using TargetScan showed no conserved binding sites for miRNAs within the short c-Myc 3 0 -UTR (467 nt), and more specifically, no potential binding sites for miR-22 were found through the whole length of c-Myc mRNA These results ruled out the possibility of a direct interaction between miR-22 and c-Myc, thus strengthening the hypothesis that miR-22 regulates E-boxcontaining c-Myc target genes through direct downregulation of MYCBP. It is not fully established how MYCBP regulates these E-box-containing genes because of growing evidence about the function of MYCBP (Furusawa et al, 2001Yukitake et al, 2002;Ishizaki et al, 2006), but there is evidence suggesting that MYCBP acts, at least in part, through modulating the transactivation activity of c-Myc to enhance the transcription of these genes (Taira et al, 1998;Sakamuro and Prendergast, 1999). Recent studies showed that some c-Myc-mediated miRNAs were implicated in tumorigenesis, embryonic stem cell differentiation and glutamine metabolism (He et al, 2005;O'Donnell et al, 2005;Dews et al, 2006;Chang et al, 2008;Sander et al, 2008;Gao et al, 2009;Lin et al, 2009;Mestdagh et al, 2009).…”

Section: Mir-22 Might Constitute a Feedback Loop With C-myc And Mycbpmentioning

confidence: 99%

Tumor-suppressive microRNA-22 inhibits the transcription of E-box-containing c-Myc target genes by silencing c-Myc binding protein

2010

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Oncogenic c-Myc has been described to modulate the expression of a subset of microRNAs (miRNAs), which include miR-22; however, the mechanism through which a miRNA controls c-Myc activity remains unclear. Here we report a novel anti-c-Myc function mediated by miR-22. Ectopically expressed miR-22 inhibited cell proliferation and anchorage-independent growth of human cancer cell lines. Microarray screening and western analyses revealed that miR-22 repressed the c-Mycbinding protein MYCBP, a positive regulator of c-Myc. Consistent with this, reporter assays showed that miR-22-mediated MYCBP gene suppression largely depends on the conserved miR-22 target site within the MYCBP 3 0 -untranslational region (3 0 UTR), implying that MYCBP mRNA is a direct miR-22 target. Depletion of MYCBP using small interfering RNA (siRNA) recapitulated the miR-22-induced anti-growth effect on tumor cells, whereas ectopically expressed MYCBP rescued cells from the growth suppression mediated by miR-22. Moreover, repression of MYCBP by miR-22 downregulated a panel of E-box-containing c-Myc target genes. Our results suggest that miR-22 acts as a tumor suppressor through direct repression of MYCBP expression and subsequent reduction of oncogenic c-Myc activities. As c-Myc inhibits the expression of miR-22, we propose a novel positive feedback loop formed by oncogenic c-Myc to accelerate cell proliferation by suppressing miR-22, a potent inhibitor of MYCBP.

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Section: Mir-22 Might Constitute a Feedback Loop With C-myc And Mycbpmentioning

confidence: 99%

Tumor-suppressive microRNA-22 inhibits the transcription of E-box-containing c-Myc target genes by silencing c-Myc binding protein

2010

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“…B, the same experiments as those described in A except for the presence of GST-AAT-1␣ or GST as a exogenous substrate were carried out. gene tend to be infertile 2 and because mitochondria are energyproducing organelles, it is possible that AMY-1 or AAT-1␣ affects the PKA activity that is used to preserve the energy necessary for fertilization. In addition to S-AKAP84/AKAP149, AMY-1 has been found to bind to many AKAPs, including other testis-specific AKAPs, and to play a positive role in cell differentiation (2,3).…”

Section: Fig 9 Phosphorylation Of Aat-1␣ By Pkamentioning

confidence: 99%

“…gene tend to be infertile 2 and because mitochondria are energyproducing organelles, it is possible that AMY-1 or AAT-1␣ affects the PKA activity that is used to preserve the energy necessary for fertilization. In addition to S-AKAP84/AKAP149, AMY-1 has been found to bind to many AKAPs, including other testis-specific AKAPs, and to play a positive role in cell differentiation (2,3). It is known that the formation and maturation of sperm are affected by several factors, including the ion gradient, various stresses, and phosphorylation signals (7-13, 25, 28 -30).…”

Section: Fig 9 Phosphorylation Of Aat-1␣ By Pkamentioning

confidence: 99%

“…Although two mRNAs, AMY-1S and AMY-1L, which are derived from the alternative usage of poly(A) adenylation signals, encode the same protein, AMY-1, AMY-1S and AMY-1L mRNAs are strongly expressed in the testis and ubiquitously in all the tissues, respectively (1). AMY-1 was found to be a stimulating factor for the initial step of erythrocyte differentiation of human K562 cells, suggesting that AMY-1 is a trigger of differentiation of K562 cells into erythrocyte cells and that AMY-1 has a function independent of or different from that of c-Myc (2). Furthermore, we have found that AMY-1 binds to AKAP149 and its splicing variant, S-AKAP84, which is expressed in the testis and is an anchor protein of cAMP-dependent protein kinase (PKA) 1 (3).…”

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confidence: 99%

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AAT-1, a Novel Testis-specific AMY-1-binding Protein, Forms a Quaternary Complex with AMY-1, A-kinase Anchor Protein 84, and a Regulatory Subunit of cAMP-dependent Protein Kinase and Is Phosphorylated by Its Kinase

Yukitake

Furusawa

Taira

et al. 2002

Journal of Biological Chemistry

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AMY-1 has been identified by us as a c-Myc-binding protein and was found to stimulate c-Myc transcription activity. AMY-1 was also found to be associated with protein kinase A anchor protein 84/149 (S-AKAP84/ AKAP149) in the mitochondria in somatic cells and sperm, suggesting that it plays a role in spermatogenesis. To determine the molecular function of AMY-1, a two-hybrid screening of cDNAs encoding AMY-1-binding proteins was carried out with AMY-1 as a bait using a human testis cDNA library, and a clone encoding a novel protein, AAT-1, was obtained. Three isoforms of AAT-1, AAT-1␣, -␤, and -␥, were found to be derived from an alternative splicing of the transcripts of the aat-1 gene, which was mapped at human chromosome 3q13-3q21. AAT-1 was found to be specifically expressed in the testis during the course of spermatogenesis and also to be present in the spermatid and mature sperm, as was AMY-1. AAT-1␣ was found to bind to and be colocalized in mitochondria with AMY-1 in human HeLa and mouse GC-1 cells. Furthermore, AAT-1␣ was found to bind to the N-terminal half of S-AKAP84/AKAP149 in a quaternary complex with AMY-1 and a regulatory subunit (RII) of cAMP-dependent kinase (PKA), in which AAT-1␣ was associated with RII via S-AKAP84/AKAP149, in rat testis and HeLa cells. It was then found that AAT-1␣ weakly stimulated a phosphorylation activity of PKA and also that AAT-1 itself was phosphorylated by PKA in vivo and in vitro. These results suggest that both AAT-1 and AMY-1 play roles in spermatogenesis.We have reported that AMY-1 (associate of Myc-1) bound to Myc box II in the N-proximal region of c-Myc, a transcriptional activation region of c-Myc (1), and stimulated E-box-dependent transcription activity of c-Myc (1). Although two mRNAs, AMY-1S and AMY-1L, which are derived from the alternative usage of poly(A) adenylation signals, encode the same protein, AMY-1, AMY-1S and AMY-1L mRNAs are strongly expressed in the testis and ubiquitously in all the tissues, respectively (1). AMY-1 was found to be a stimulating factor for the initial step of erythrocyte differentiation of human K562 cells, suggesting that AMY-1 is a trigger of differentiation of K562 cells into erythrocyte cells and that AMY-1 has a function independent of or different from that of c-Myc (2). Furthermore, we have found that AMY-1 binds to AKAP149 and its splicing variant, S-AKAP84, which is expressed in the testis and is an anchor protein of cAMP-dependent protein kinase (PKA) 1 (3). AKAP is a protein that translocates PKA to the specific sites where the individual PKA works, and more than 10 AKAPs have so far been identified (4 -6). Of the identified AKAPs, S-AKAP84 and AKAP149 have been found to anchor PKA to the mitochondria to phosphorylate the target proteins in the testis and other cells, respectively. Although some target proteins to be phosphorylated by PKA in the mitochondria have been identified, the physiological significance of their phosphorylation is not clear. It has been reported that tyrosine phosphorylation of proteins plays...

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“…The anti-rSjAMY-1 sera were collected from rats immunized with the recombinant protein, and these rats developed specific antibodies to titers >3.6x10 6 , as determined by ELISA (data not shown). The native SjAMY-1 in SWAP and rSjAMY-1 were recognized by anti-rSjAMY-1 sera as shown in Fig.…”

Section: The Recognition Of Native and Rsjamy-1 By Anti-rsjamy-1 Seramentioning

confidence: 99%

Molecular cloning and tissue distribution of a Schistosoma japonicum gene encoding AMY-1

Tang³

et al. 2011

Mol Med Report

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Abstract.It is well known that the mammalian associate of Myc-1 (AMY-1) plays a significant role in spermatogenesis or cellular differentiation. A full-length complementary DNA (cDNA) encoding AMY-1 of Schistosoma japonicum (SjAMY-1) was identified and isolated from a cDNA library. The gene contained an open reading frame of 315 nucleotides, encoding 105 amino acids. Sequence analysis showed that SjAMY-1 shares 65.7% homology with Homo sapiens AMY-1 amino acids and contains a conserved domain from the AMY-1 family. In this study, we cloned and expressed a recombinant SjAMY-1 (rSjAMY-1) with a molecular size of 14 kDa. The native SjAMY-1 in soluble worm antigen was identified by anti-rSjAMY-1 sera in the Western blot analysis, which demonstrated the presence of this protein in the parasite. Immunofluorescence studies indicated a localization of SjAMY-1 in various tissues and organs including the tegument and subtegumental muscles in adult worms, the ventral sucker in cercariae and the internal structures of eggs. Given the key roles of mammalian AMY-1 in cell proliferation and differentiation, the characterization of SjAMY-1 may allow for a better understanding of the development of S. japonicum.

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AMY-1 is a trigger for the erythrocyte differentiation of K562 cells.

Cited by 12 publications

References 0 publications

Tumor-suppressive microRNA-22 inhibits the transcription of E-box-containing c-Myc target genes by silencing c-Myc binding protein

Tumor-suppressive microRNA-22 inhibits the transcription of E-box-containing c-Myc target genes by silencing c-Myc binding protein

AAT-1, a Novel Testis-specific AMY-1-binding Protein, Forms a Quaternary Complex with AMY-1, A-kinase Anchor Protein 84, and a Regulatory Subunit of cAMP-dependent Protein Kinase and Is Phosphorylated by Its Kinase

Molecular cloning and tissue distribution of a Schistosoma japonicum gene encoding AMY-1

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