Revisiting purine-histidine cross-pathway regulation in Saccharomyces cerevisiae:: A central role for a small molecule

被引:73
作者
Rébora, K [1 ]
Laloo, B [1 ]
Daignan-Fornier, B [1 ]
机构
[1] Univ Bordeaux 2, CNRS, Inst Biochim & Genet Cellulaires, UMR 5095, F-33077 Bordeaux, France
关键词
D O I
10.1534/genetics.104.039396
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Because some metabolic intermediates are involved in more than one pathway, crosstalk between pathways is crucial to maintaining homeostasis. AMP and histidine biosynthesis pathways are coregulated at the transcriptional level in response to adenine availability. 5'-Phosphoribosyl-4-carboxamide-5-aminoimidazole (AICAR), a metabolic intermediate at the crossroads between these two pathways, is shown here to be critical for activation of the transcriptional response in the absence of adenine. In this study, we show that both AMP and histidine pathways significantly contribute to AICAR synthesis. Furthermore, we show that upregulation of the histidine pathway clearly interferes with regulation of the AMP pathway, thus providing an explanation for the regulatory crosstalk between these pathways. Finally, we revisit the histidine auxotrophy of ade3 or ade16 ade17 mutants. Interestingly, overexpression of PMU1, encoding a potential phosphomutase, partially suppresses the histidine requirement of an ade3 ade16 ade17 triple mutant, most probably by reducing the level of AICAR in this mutant. Together our data clearly establish that AICAR is not just a metabolic intermediate but also acts as a true regulatory molecule.
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页码:61 / 70
页数:10
相关论文
共 41 条
[31]   Yeast AMP pathway genes respond to adenine through regulated synthesis of a metabolic intermediate [J].
Rébora, K ;
Desmoucelles, C ;
Borne, F ;
Pinson, B ;
Daignan-Fornier, B .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (23) :7901-7912
[32]  
SHEDLOVSKY AE, 1962, J BIOL CHEM, V237, P3725
[33]  
SHEDLOVSKY AE, 1962, J BIOL CHEM, V237, P3731
[34]  
SHERMAN F, 1986, METHODS YEAST GENET
[35]   Amino acid and adenine cross-pathway regulation act through the same 5'-TGACTC-3' motif in the yeast HIS7 promoter [J].
Springer, C ;
Kunzler, M ;
Balmelli, T ;
Braus, GH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (47) :29637-29643
[36]   Inhibition of glucocorticoid-induced apoptosis with 5-aminoimidazole-4-carboxamide ribonucleoside, a cell-permeable activator of AMP-activated protein kinase [J].
Stefanelli, C ;
Stanic, I ;
Bonavita, F ;
Flamigni, F ;
Pignatti, C ;
Guarnieri, C ;
Caldarera, CM .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 243 (03) :821-826
[37]   CHARACTERIZATION OF 5'-AMP-ACTIVATED PROTEIN-KINASE IN HUMAN LIVER USING SPECIFIC PEPTIDE-SUBSTRATES AND THE EFFECTS OF 5'-AMP ANALOGS ON ENZYME-ACTIVITY [J].
SULLIVAN, JE ;
CAREY, F ;
CARLING, D ;
BERI, RK .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1994, 200 (03) :1551-1556
[38]   INVITRO TRANSCRIPTIONAL ACTIVATION BY A METABOLIC INTERMEDIATE - ACTIVATION BY LEU3 DEPENDS ON ALPHA-ISOPROPYLMALATE [J].
SZE, JY ;
WOONTNER, M ;
JAEHNING, JA ;
KOHLHAW, GB .
SCIENCE, 1992, 258 (5085) :1143-1145
[39]   Characterization of two 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase isozymes from Saccharomyces cerevisiae [J].
Tibbetts, AS ;
Appling, DR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (27) :20920-20927
[40]   Regulation of hisHF transcription of Aspergillus nidulans by adenine and amino acid limitation [J].
Valerius, O ;
Draht, O ;
Kübler, E ;
Adler, K ;
Hoffmann, B ;
Braus, GH .
FUNGAL GENETICS AND BIOLOGY, 2001, 32 (01) :21-31