Nm23/PuF Does Not Directly Stimulate Transcription through the CT Element in Vivo

Michelotti, Emil F.; Sanford, Suzanne; Freije, José M.P.; MacDonald, Nicholas J.; Steeg, Patricia S.; Levens, David

doi:10.1074/jbc.272.36.22526

Cited by 41 publications

(23 citation statements)

References 35 publications

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“…These factors also bind to the HIS4 promoter and are responsible for expression of HIS4 under limiting conditions (55). Similarly, the transcriptional activation capacity of Nm23-H2 is still a matter of controversy, and its putative function as a cofactor modifying trans-acting factors during tumor suppression has been discussed (56).…”

Section: Discussionmentioning

confidence: 99%

UV-responsive Genes of Arabidopsis Revealed by Similarity to the Gcn4-mediated UV Response in Yeast

Zimmermann

Baumann

Jaekel

et al. 1999

Journal of Biological Chemistry

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A UV response that involves the Ras proteins and AP-1 transcription factors has recently been described in mammals and yeast. To test whether an equivalent response exists in plants, we monitored the expression of Arabidopsis histidinol dehydrogenase gene (HDH), a homologue of the yeast HIS4 gene, which is strongly induced by UV light and is a target of the transcriptional activator Gcn4. We show that HDH mRNA levels increase specifically in response to UV-B light. Only small increases were detected upon exposure to other wavelengths. To isolate plant genes involved in this UV response, a gcn4 mutant was transfected with an Arabidopsis thaliana cDNA library. A new type of nucleotide diphosphate kinase (NDPK Ia) with a significant homology to the human tumor suppressor protein Nm23 rescued the gcn4 phenotype. NDPK Ia specifically binds to the HIS4 promoter in vitro and induces HIS4 transcription in yeast. In Arabidopsis, the NDPK Ia protein is located in the nucleus and cytosol. Expression studies in seedlings revealed that the level of NDPK Ia mRNA, like that of HDH, increases in response to UV-B light. It appears that NDPK Ia and HDH are components of a novel UV-responsive pathway in A. thaliana.

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Section: Discussionmentioning

confidence: 99%

UV-responsive Genes of Arabidopsis Revealed by Similarity to the Gcn4-mediated UV Response in Yeast

Zimmermann

Baumann

Jaekel

et al. 1999

Journal of Biological Chemistry

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“…• Nm23-H2 did not function as a c-myc transcription factor using multiple promoter activity constructs (Michelotti et al 1997, Chae et al 1998). …”

Section: Concernsmentioning

confidence: 99%

“…The arguments against this activity have been numerous and broad. Briefly, regulation of c-myc transcription by NDPK/ Nm23 was not observed using traditional promoter-driven fusion protein transcriptional assays used throughout the myc field (Michelotti et al 1997), NDPK/Nm23 was reported to bind to any single-stranded DNA without specificity (Hildebrandt et al 1995;Agou et al 1999), and the DNA cleavage activity postulated for remodeling of the quadraplex was a contaminant (Dexheimer et al 2009). Another paper on the G-quadraplex binding activity of NDPK/Nm23 was published in a high-ranking journal and later retracted (Grand et al 2004).…”

Section: Concernsmentioning

confidence: 99%

A critical evaluation of biochemical activities reported for the nucleoside diphosphate kinase/Nm23/Awd family proteins: opportunities and missteps in understanding their biological functions

Steeg

Zollo

Wieland

2011

Naunyn-Schmiedeberg's Arch Pharmacol

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“…This later complex is responsible for the newly described phosphotransferase function of nm23-H1 (Engel et al, 1995(Engel et al, , 1998Wagner et al, 1997). Other studies have shown that the catalytic activity of NDPKs can be dissociated from the antimetastatic function of nm23-H1 and from the indirect enhancement of c-myc expression by nm23-H2 (Berberich and Postel, 1995;Hartsough and Steeg, 1998;Michelotti et al, 1997;Postel et al, 1993).…”

Section: Introductionmentioning

confidence: 95%

“…The second human NDPK, nm23-H2, acts indirectly as an enhancer of c-myc expression (Berberich and Postel, 1995;Michelotti et al, 1997;Postel et al, 1993). Similarly, nm23-H3 (DR) is di erentially expressed in blastic transformation of chronic myelogenous leukemia (Venturelli et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Evidence for interaction between human PRUNE and nm23-H1 NDPKinase

et al. 1999

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We have isolated a human and murine homologue of the Drosophila prune gene through dbEST searches. The gene is ubiquitously expressed in human adult tissues, while in mouse developing embryos a high level of expression is con®ned to the nervous system particularly in the dorsal root ganglia, cranial nerves, and neural retina. The gene is composed of eight exons and is located in the 1q21.3 chromosomal region. A pseudogene has been sequenced and mapped to chromosomal region 13q12. PRUNE protein retains the four characteristic domains of DHH phosphoesterases. The synergism between prune and awd K-pn in Drosophila has led various authors to propose an interaction between these genes. However, such an interaction has never been supported by biochemical data. By using interaction-mating and in vitro co-immunoprecipitation experiments, we show for the ®rst time the ability of human PRUNE to interact with the human homologue of awd protein (nm23-H1). In contrast, PRUNE is impaired in its interaction with nm-23-H1-S120G mutant, a gain-of-function mutation associated with advanced neuroblastoma stages. Consistently, PRUNE and nm23-H1 proteins partially colocalize in the cytoplasm. The data presented are consistent with the view that PRUNE acts as a negative regulator of the nm23-H1 protein. We discuss how PRUNE regulates nm23-H1 protein and postulate possible implications of PRUNE in neuroblastoma progression.

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Nm23/PuF Does Not Directly Stimulate Transcription through the CT Element in Vivo

Cited by 41 publications

References 35 publications

UV-responsive Genes of Arabidopsis Revealed by Similarity to the Gcn4-mediated UV Response in Yeast

UV-responsive Genes of Arabidopsis Revealed by Similarity to the Gcn4-mediated UV Response in Yeast

A critical evaluation of biochemical activities reported for the nucleoside diphosphate kinase/Nm23/Awd family proteins: opportunities and missteps in understanding their biological functions

Evidence for interaction between human PRUNE and nm23-H1 NDPKinase

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