Disease relevance of HMG1

• In contrast, the hmg1 mutant exhibited dwarfing, early senescence, and sterility [1].
• The five HMG1-like proteins were expressed in Escherichia coli and purified [2].
• Overexpression of 3-hydroxy-3-methylglutaryl coenzyme A reductase did not prevent chlorosis in plants overexpressing FPS1L, but did rescue accelerated senescence of detached leaves and restored wild-type levels of cytokinins [3].
• All three transgenes (35S-AtHMG1, 35S-AtHMG1m and 35S-AtScHMG1) were under the control of a cauliflower mosaic virus 35S RNA promoter [4].

High impact information on HMG1

• Expression of the Arabidopsis HMG2 gene, encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase, is restricted to meristematic and floral tissues [5].
• The synthesis of mevalonate, which is considered the first rate-limiting step in isoprenoid biosynthesis, is catalyzed by the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR; EC 1.1.1.34) [5].
• The N-terminal end and the C-terminal catalytic domain of Arabidopsis HMGR are positioned on the cytosolic side of the membrane, whereas only a short hydrophilic sequence is exposed to the lumen [6].
• Our results suggest that the plant HMGR isoforms known to date are primarily targeted to the endoplasmic reticulum and have the same topology in the membrane [6].
• Differential induction and suppression of potato 3-hydroxy-3-methylglutaryl coenzyme A reductase genes in response to Phytophthora infestans and to its elicitor arachidonic acid [7].

Chemical compound and disease context of HMG1

• WT plants treated exogenously with inhibitors of sterol biosynthesis had similar gene expression and sterility characteristics as the hmg1 mutants [1].

Biological context of HMG1

• HMG1 and HMG2 consist of four exons and three small introns that interrupt the coding sequence at equivalent positions [8].
• These findings suggest that HMG1 plays a critical role in triterpene biosynthesis, and that sterols and/or triterpenoids contribute to cell elongation, senescence, and fertility [1].
• The similarity between the two encoded proteins (HMGR1 and HMGR2) is restricted to the regions corresponding to the membrane and the catalytic domains [8].
• By using promoter/reporter gene fusions we also demonstrate that this reaction is mediated by cis-acting elements that reside in the Arabidopsis HMG1 promoter and, therefore, is likely to be controlled at the transcriptional level [9].
• The Arabidopsis HMG1-like proteins contain an HMG domain as a common feature, but outside this conserved DNA-binding motif the amino acid sequences are significantly different indicating that this protein family displays a greater structural variability in plants than in other eukaryotes [2].

Anatomical context of HMG1

• Our results suggest that the endoplasmic reticulum is the only cell compartment for the targeting of HMGR in Arabidopsis and support the hypothesis that in higher plants the formation of mevalonate occurs solely in the cytosol [8].
• By using a coupled in vitro transcription-translation assay, we show that both HMGR1 and HMGR2 are cotranslationally inserted into endoplasmic reticulum-derived microsomal membranes [8].
• Taken together, these data indicate that light-mediated control of the HMG1 gene is mediated by a regulatory circuit that monitors aspects of both spectral quality and fluence and involves either multiple photoreceptors or a single photoreceptor that is differentially sensitive to both blue and red light [9].
• Taken together, the results reveal that endogenous Arabidopsis HMGR is localized at steady state within ER as expected, but surprisingly also predominantly within spherical, vesicular structures that range from 0.2- to 0.6-microm diameter, located in the cytoplasm and within the central vacuole in differentiated cotyledon cells [10].
• The results in this paper represent the first evidence that a higher plant HMGR is regulated by direct phosphorylation, at least in a cell-free system [11].

Associations of HMG1 with chemical compounds

• The sterol levels in hmg1 mutants were lower than in the WT [1].
• The hmg1 and hmg2 mutants were both more sensitive than the wild type (WT) to lovastatin, an inhibitor of HMGR [1].
• In contrast, changes in HMG1 mRNA levels were not observed in response to brief light pulses of any spectrum, suggesting that continuous illumination is required for sustained and maximal suppression of HMG coenzyme A reductase expression [9].
• RNA gel blot analyses using gene-specific probes showed that hmg1 was strongly induced in tuber tissue by wounding, but the wound induction was strongly suppressed by treatment of the tissue with the fungal elicitor arachidonic acid or by inoculation with an incompatible or compatible race of the fungal pathogen Phytophtora infestans [7].
• Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is essential for the biosynthesis of sesquiterpenoid phytoalexins and steroid derivatives in Solanaceous plants following stresses imposed by wounding and pathogen infection [7].

Other interactions of HMG1

• HMG1 mRNA is detected in all tissues, whereas the presence of HMG2 mRNA is restricted to young seedlings, roots, and inflorescences [8].
• Expression of senescence-associated genes 12 (SAG12), a marker gene for senescence, was induced in the hmg1 mutant at an earlier stage than in the WT [1].
• Since three enzymes, 3-hydroxy-3-methylglutaryl CoA reductase, farnesyl diphosphate synthase, and lanosterol synthase, have been functionally characterized in planta, we reviewed recent progress on these enzymes [12].
• In addition, NtMEK2-SIPK/WIPK cascade appears to control the expression of 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) and l-phenylalanine ammonia lyase (PAL), two defense genes encoding key enzymes in the phytoalexin and salicylic acid biosynthesis pathways [13].
• PKIII was also very active in phosphorylating and inactivating Arabidopsis (Landsberg erecta) 3-hydroxy-3-methylglutaryl-coenzyme A reductase 1 (HMGR1) [14].

Analytical, diagnostic and therapeutic context of HMG1

• Reverse-transcribed PCR suggested that the five HMG1-like genes are simultaneously expressed in Arabidopsis leaves and suspension culture cells [2].
• Northern blot analysis indicated that the HMGR1 transcript of 2.4 kb is more highly-expressed in laticifer than in leaf [15].
• The apparent molecular mass of Hevea HMGR was estimated in western blot analysis to be 59 kDa [15].
• Sequence analysis revealed that these clones fall into two different classes, HMGR1 and HMGR2 [15].

References