Efficacy and safety of abiraterone acetate plus prednisolone in patients with early metastatic castration-resistant prostate cancer who failed first-line androgen-deprivation therapy: a single-arm, phase 4 study.

AIM: The aim was to evaluate the efficacy and safety of abiraterone acetate plus prednisolone in patients with chemotherapy-naïve early metastatic castration-resistant prostate cancer who failed first-line androgen deprivation therapy. METHODS: Patients with early metastatic castration-resistant prostate cancer with confirmed prostate-specific antigen progression within 1-year or prostate-specific antigen progression without having normal prostate-specific antigen level (<4.0 ng/mL) during first-line androgen deprivation therapy were enrolled and administered abiraterone acetate (1000 mg) plus prednisolone (10 mg). A minimum of 48 patients were required according to Simon's minimax design. The primary endpoint was prostate-specific antigen response rate (≥50% prostate-specific antigen decline by 12 weeks), secondary endpoints included prostate-specific antigen progression-free survival and overall survival. Safety parameters were also assessed. RESULTS: For efficacy, 49/50 patients were evaluable. Median age was 73 (range: 55-86) years. The median duration of initial androgen deprivation therapy was 32.4 (range: 13.4-84.1) weeks and 48 patients experienced prostate-specific antigen progression within 1-year after initiation of androgen deprivation therapy. prostate-specific antigen response rate was 55.1% (95% confidence interval: 40.2%-69.3%), median prostate-specific antigen-progression-free survival was 24.1 weeks, and median overall survival was 102.9 weeks (95% confidence interval: 64.86 not estimable [NE]). Most common adverse event was nasopharyngitis (15/50 patients, 30.0%). The most common ≥grade 3 adverse event was alanine aminotransferase increased (6/50 patients, 12.0%). CONCLUSIONS: Abiraterone acetate plus prednisolone demonstrated a high prostate-specific antigen response rate of 55.1%, suggesting tumor growth still depends on androgen synthesis in patients with early metastatic castration-resistant prostate cancer. However, prostate-specific antigen-progression-free survival was shorter than that reported in previous studies. Considering the benefit-risk profile, abiraterone acetate plus prednisolone would be a beneficial treatment option for patients with chemotherapy-naive metastatic prostate cancer who show early castration resistance.

Prediction of hemorrhagic transformation after acute thrombolysis following major artery occlusion using relative ADC ratio: A retrospective study.

BACKGROUND: The relative apparent diffusion coefficient (ADC) ratio can be used to evaluate the extent of ischemia. We investigated the risk factors for, and correlation between, relative ADC ratio and hemorrhagic transformation (HT) after thrombolysis. METHODS: This single-center, retrospective study involved 105 patients with acute occlusion of the anterior circulation. Relative ADC ratio was calculated as the ratio of ADC pixel values, within the affected territory to ADC pixel values in the contralateral normal region. HT was determined by computed tomography and T2* weighted magnetic resonance imaging after endovascular revascularization. RESULTS: Data for 80 of the 105 patients were analyzed. Comparing the number of patients between the HT group (n=25) and the non-HT group (n=55), a significant difference was noted in tissue plasminogen activator (tPA) use (P=0.028), time from onset to reperfusion ≥380min (P<0.001), fluid-attenuated inversion recovery (FLAIR) hyperintensity (P=0.009), and relative ADC ratio<0.650 (P<0.001). Multivariable logistic regression analysis identified relative ADC ratio<0.650 as the only independent predictor of HT (odds ratio 7.79; 95% confidence interval 2.22-27.3; P=0.001). Twenty-nine patients (including 20 in the HT group) had a relative ADC ratio<0.650. Multivariable logistic regression analysis identified use of tPA as the only independent predictor of HT (odds ratio 13.8; 95% confidence interval 1.35-125.5; P=0.010). CONCLUSIONS: Relative ADC ratio<0.650 with use of tPA may be important for predicting HT.

Relationship between vegetable and carotene intake and risk of prostate cancer: the JACC study.

BACKGROUND: We examined the associations of intakes of vegetables and carotenes with risk of prostate cancer in Japanese. METHODS: A total of 15,471 Japanese men participating in the Japan Collaborative Cohort study completed a questionnaire including food intake. Of them, 143 incident prostate cancers were documented. We examined the associations stated above by using Cox proportional hazard model. RESULTS: Vegetable intake was not associated with the risk of prostate cancer, but so was dietary alpha-carotene intake. The multivariable hazard ratio (95%CI) in the secondary highest and highest quintiles of alpha-carotene intake was 0.50 (0.26-0.98) (P=0.043) and 0.46 (0.22-0.97) (P=0.041) (P for trend=0.224), respectively. Beta-carotene intake was not associated with the risk of prostate cancer. CONCLUSION: Alpha-carotene intake was associated with lower risk of prostate cancer among Japanese.

Clinical effects of kestose, a prebiotic oligosaccharide, on the treatment of atopic dermatitis in infants.

BACKGROUND: Oligosaccharides may have beneficial properties of the prevention of atopic dermatitis (AD). Kestose, a fructo-oligosaccharide, stimulates the activity of bifidobacteria. OBJECTIVE: To assess the clinical effect of kestose on the treatment of AD in infants. METHODS: A randomized, double-blind, placebo-controlled trial was carried out using 15 and 14 infants with AD in the kestose group and placebo groups, respectively. One to 2 g kestose and maltose were administered to the subjects in the kestose and placebo groups, respectively, everyday for 12 weeks. Clinical evaluations of AD using Severity Scoring of Atopic Dermatitis (SCORAD) and the enumeration of bifidobacteria in the feces using real-time PCR were performed at Weeks 0, 6, and 12. RESULTS: The medians of the SCORAD score were significantly lower in the kestose group than in the placebo group on both Week 6 (25.3 vs. 36.4; P=0.004) and Week 12 (19.5 vs. 37.5; P<0.001). No significant correlation was found between the improvement of the SCORAD score and the count of bifidobacteria. CONCLUSION: Kestose was found to exert a beneficial effect on the clinical symptoms in infants with AD. The mechanism how does kestose improve the symptoms of AD remains to be elucidated.

A protein that binds to a cis-acting element of wheat histone genes has a leucine zipper motif.

The structure and function of transcription factors of higher plants was studied by isolating cDNA clones encoding a wheat sequence-specific DNA binding protein. A hexameric nucleotide motif, ACGTCA, is located upstream from the TATA box of several plant histone genes. It has been suggested that this motif is essential for efficient transcription of the wheat histone H3 gene. A wheat nuclear protein, HBP-1 (histone DNA binding protein-1), which specifically binds to the hexameric motif, has previously been identified as a putative transcription factor. A cDNA clone encoding HBP-1 has been isolated on the basis of specific binding of HBP-1 to the hexameric motif. The deduced amino acid sequence indicates that HBP-1 contains the leucine zipper motif, which represents a characteristic property of several eukaryotic transcription factors.

Non-Mendelian inheritance of macronuclear mutations is gene specific in Paramecium tetraurelia.

Paramecium tetraurelia contains two types of nuclei, a diploid germinal micronucleus and a large transcriptionally active macronucleus. The macronuclear genome is formed from the micronuclear DNA during sexual reproduction. Previous studies have shown that the processing of the A-type variable surface protein gene during formation of a new macronucleus is dependent on the presence of the A gene in the old macronucleus. It is not clear if this is a general feature that controls the formation of the Paramecium macronuclear genome or a unique feature of the A locus. Using micronuclear transplantation, we have constructed a strain that has a wild-type micronucleus but has macronuclear deletions of the A- and B-type surface protein genes. Neither the A nor the B gene is incorporated into the new macronucleus after sexual reproduction. Macronuclear transformation of this strain with the B gene rescues the B-gene deletion after formation of the next macronucleus but has not effect on the A deletion. Similarly, transformation with the A gene shows gene-specific rescue for A but not B. The effect of the old macronucleus on the processing of the new macronucleus results in a pattern of non-Mendelian inheritance of both macronuclear deletions. Progeny from the wild-type exconjugant are all wild type, and progeny from the A- B- exconjugant are mutant. The features of this A- B- non-Mendelian mutant demonstrate that the regulation of macronuclear DNA processing is gene specific, and our results open the possibility that this type of regulation affects many regions of the Paramecium genome.

DT-diaphorase as a critical determinant of sensitivity to mitomycin C in human colon and gastric carcinoma cell lines.

Mitomycin C (MMC), a known cytotoxic agent, requires cellular enzyme-mediated activation for effective antitumor activity. To study the bioreductive enzymes responsible for MMC activation in tumor cells, we examined the enzyme activities of DT-diaphorase (DTD) and NADPH:cytochrome P-450 reductase in 13 colon and gastric carcinoma cell lines and then compared these activities to the respective cellular MMC sensitivity. We found that cell lines with nonexistent or marginal DTD activity, such as St-4 and MKN7, showed resistance to MMC, in comparison to cell lines with DTD activity ranging from 210 to 1420 nmol/min/mg protein. No correlation was found between NADPH:cytochrome P-450 reductase activity and MMC sensitivity in these cell lines. To confirm the role of DTD in cellular MMC sensitivity, we constructed an expression vector containing NQO1, a gene that codes for DTD, and transfected the vector into St-4 cells expressing no DTD activity. Several transfectant clones with DTD activity from 144 to 2085 nmol/min/mg protein were obtained. All of the transfectants showed 5-10-fold higher sensitivity to MMC compared to the parental St-4 cells. Consistent with the MMC sensitivity, we also found that MMC-DNA adduct was formed more extensively in the NQO1 transfectants than in the St-4 cells. These results indicate that DTD activity is required for effective cytotoxicity of MMC in colon and gastric carcinoma cells.

Molecular characterization of a cDNA encoding a novel small GTP-binding protein from Arabidopsis thaliana.

A full-length cDNA clone encoding a novel Rab protein AtRab alpha of the monomeric small GTP-binding protein family has been isolated from Arabidopsis thaliana. AtRab alpha has 210 amino acids with a calculated molecular mass of 23.3 kDa. The highest homology was found to Rab1x and Rab1y from Lotus japonicus. Southern blot analysis of genomic DNA indicated that AtRab alpha was encoded by a single copy gene. Northern blot analysis showed that expression of the AtRab alpha mRNA was rich in stems and roots, but poor in leaves and flowers, which is different from the expression pattern of other Arabidopsis Rab genes.

Transport of cyclosporin A across the brain capillary endothelial cell monolayer by P-glycoprotein.

P-glycoprotein, a multidrug transporter protein, exists in the brain capillary endothelium. To study the function of P-glycoprotein in brain capillary endothelium as a barrier against cyclosporin A, we examined the interaction of cyclosporin A with P-glycoprotein expressed in cultured brain capillary endothelial cells (MBEC4). P-glycoprotein of MBEC4 specifically bound [125I]iodoaryl azidoprazosin, and the binding was inhibited by cyclosporin A and vincristine. Intracellular accumulation of cyclosporin A in MBEC4 was about one-third the amount accumulated in mouse aortic endothelial cells (MAEC3), a cell line that did not express P-glycoprotein. The reduced accumulation of cyclosporin A in MBEC4 was increased by verapamil, a competitive inhibitor of transport function of P-glycoprotein. Cyclosporin A was preferentially transported from basal to apical side when the cell monolayer of MBEC4 was formed; however this transendothelial transport was not observed across cell monolayer of MAEC3. Verapamil inhibited the transendothelial transport of cyclosporin A across the MBEC4 monolayer. Thus P-glycoprotein in brain capillary endothelium could transport cyclosporin A across the endothelium from the basal to the apical side. These observations suggest that P-glycoprotein is involved in the complex function of the blood-brain barrier as a secretory detoxifying transporter of cyclosporin A.

A mutation in Paramecium tetraurelia reveals functional and structural features of developmentally excised DNA elements.

The excision of internal eliminated sequences (IESs) from the germline micronuclear DNA occurs during the differentiation of a new macronuclear genome in ciliated protozoa. In Paramecium, IESs are generally short (28-882 bp), AT rich DNA elements that show few conserved sequence features with the exception of an inverted-terminal-repeat consensus sequence that has similarity to the ends of mariner/Tcl transposons (KLOBUTCHER and HERRICK 1995). We have isolated and analyzed a mutant cell line that cannot excise a 370-bp IESs (IES2591) from the coding region of the 51A variable surface protein gene. A single micronuclear C to T transition within the consensus sequence prevents excision. The inability to excise IES259 I has revealed a 28-bp IES inside the larger IES, suggesting that reiterative integration of these elements can occur. Together, the consensus sequence mutation and the evidence for reiterative integration support the theory that Paramecium IESs evolved from transposable elements. Unlike a previously studied Paramecium IES, the presence of this IES in the macronucleus does not completely inhibit excision of its Mild-type micronuclear copy through multiple sexual generations.

Catalytic asymmetric syntheses and biological activities of singly dehydroxylated 19-nor-1alpha,25-dihydroxyvitamin D(3) A-ring analogs in cancer cell differentiation and apoptosis.

BACKGROUND: 1alpha,25-Dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) has been shown to modulate not only proliferation and differentiation, but also apoptosis in malignant cells, indicating that it could be useful for treating cancer. Little information is available concerning the structural motifs of the 1alpha, 25(OH)(2)D(3) molecule responsible for modulation of differentiation and apoptosis, however. We set out to synthesize singly dehydroxylated A-ring analogs of 19-nor-1alpha,25(OH)(2)D(3) in a catalytic asymmetric fashion, and to investigate their biological activities in leukemia HL-60 cells. RESULTS: A series of singly dehydroxylated 19-nor-1alpha,25-dihydroxyvitamin D(3) A-ring analogs were synthesized using a combinatiorial sequence of regioselective propiolate-ene reaction and catalytic asymmetric carbonyl-ene cyclization. Surprisingly, the analogs could be clearly divided into two categories; one group, bearing 1alpha-hydroxy or 3beta-hydroxy groups in the A-ring, were potent differentiators and the second group, bearing 1beta-hydroxy or 3alpha-hydroxy groups, were potent stimulators of apoptosis. CONCLUSIONS: We have clearly identified the structural motifs of 19-nor-1alpha,25(OH)(2)D(3) analogs responsible for differentiation and apoptosis in HL-60 cells. These findings will provide useful information not only for development of therapeutic agents for treatment of leukemia and other cancers, but also for structure-function studies of 1alpha,25(OH)(2)D(3).

Spontaneous healing of chyle leakage after lymphangiography.

We report a 34-year-old man with the complication of chylous ascites after retroperitoneal lymphadenectomy that was refractory to various conservative therapies. Because surgical treatment for chylous ascites was considered, lymphangiography was performed to identify the area of leakage of chyle, after which the chylous ascites spontaneously healed.

Impact of maternal bifidobacteria and the mode of delivery on Bifidobacterium microbiota in infants.

The aim of this study is to examine the influence of maternal intestinal and vaginal bifidobacteria on the colonisation of bifidobacteria in the gut of infants. Faecal samples from 120 healthy pregnant mothers within 1 month of delivery and from their infants at 1 month of age and 98 vaginal swabs from the mothers at the time of delivery were collected at a maternity hospital in Chiang Mai, Thailand. The faecal and vaginal samples were assayed by real-time PCR assays to detect Bifidobacterium species and to estimate the bifidobacterial copy numbers. After adjusting for the numbers of each Bifidobacterium species, delivery mode, and antibiotic use in infants by the age of 1 month, total counts of bifidobacteria in the mothers' faeces were associated with increased copy numbers of bifidobacteria in the faeces of breastfed infants. A caesarean section was also significantly associated with a decrease in the copy numbers of bifidobacteria in the faeces of infants. No significant correlation was found between the bifidobacterial copies of the vaginal swabs and those of the infants' faeces. The intestinal bifidobacterial status of exclusively breastfed infants was significantly positive affected by vaginal delivery and high bifidobacterial copy numbers in their mothers' gut.

The 3-second auditory conditioned stimulus is a more effective stressor than the 20-second auditory conditioned stimulus in male rats.

Using fear-conditioning model, we have used a 3-s auditory conditioned stimulus (CS) as a stressor and observed fear and stress responses during a specific experimental period regardless of the presence or absence of the CS. Because the CS was extremely short compared with the experimental period, we observed responses primarily in the absence of the CS. In contrast, most studies in the literature have analyzed responses in the presence of the CS. Therefore, the characteristics of fear and stress responses in the absence of the CS remain to be clarified. To clarify this, we compared the characteristics of fear and stress responses elicited by a 3-s auditory CS with those observed during a 20-s auditory CS. The basolateral complex of the amygdala (BLA), but not the bed nucleus of the stria terminalis (BNST), participated in the fear response elicited by the 3-s CS, whereas both the BLA and BNST were involved in the response observed during the 20-s CS. Additional analyses revealed that the BNST participated in the fear response during the 20-s CS when the CS was paired with a 0.75-mA, but not with a 0.9-mA, foot shock, and to the contextual CS. In addition, the fear response elicited by the 3-s CS was more resistant to extinction than that during the 20-s CS. Finally, the 3-s CS produced more intense freezing and corticosterone secretion than the 20-s CS. On the basis of these characteristics, we conclude that the 3-s auditory CS is a more effective stressor than the 20-s auditory CS. Our findings also suggest that foot shock intensity is an additional determinant in the type of fear response induced by the CS.

Impact of p53 Status on Radiosensitization of Tumor Cells by MET Inhibition-Associated Checkpoint Abrogation.

UNLABELLED: Signaling via the MET receptor tyrosine kinase has been implicated in crosstalk with cellular responses to DNA damage. Our group previously demonstrated that MET inhibition in tumor cells with deregulated MET activity results in radiosensitization via downregulation of the ATR-CHK1-CDC25 pathway, a major signaling cascade responsible for intra-S and G2-M cell-cycle arrest following DNA damage. Here we aimed at studying the potential therapeutic application of ionizing radiation in combination with a MET inhibitor, EMD-1214063, in p53-deficient cancer cells that harbor impaired G1-S checkpoint regulation upon DNA damage. We hypothesized that upon MET inhibition, p53-deficient cells would bypass both G1-S and G2-M checkpoints, promoting premature mitotic entry with substantial DNA lesions and cell death in a greater extent than p53-proficient cells. Our data suggest that p53-deficient cells are more susceptible to EMD-1214063 and combined treatment with irradiation than wild-type p53 lines as inferred from elevated γH2AX expression and increased cytotoxicity. Furthermore, cell-cycle distribution profiling indicates constantly lower G1 and higher G2-M population as well as higher expression of a mitotic marker p-histone H3 following the dual treatment in p53 knockdown isogenic variant, compared with the parental counterpart. IMPLICATIONS: The concept of MET inhibition-mediated radiosensitization enhanced by p53 deficiency is of high clinical relevance, as p53 is frequently mutated in numerous types of human cancer. The current data point for a therapeutic advantage for an approach combining MET targeting along with DNA-damaging agents for MET-positive/p53-negative tumors.

Differential suppression of the outer and inner zones of the adrenal cortex of the guinea pig.

To examine the regulation of the zona fasciculata and the zona reticularis of the guinea pig adrenal cortex, animals were placed on a chronic regimen of dexamethasone. Changes in adrenal zonal weight, cholesterol side-chain cleavage activity, and tissue and serum steroid concentrations were measured after 1 month of dexamethasone administration. With dexamethasone treatment, the weight of the outer zone (glomerulosa/fasciculata) decreased significantly, while the weight of the inner zone (reticularis) did not change. Cholesterol side-chain cleavage activity in mitochondria isolated from the outer zone also declined significantly, while a similar activity in the inner zone did not change. The serum cortisol concentration in response to dexamethasone administration decreased by 85%, as did the concentrations of cortisol and progesterone in the outer zone; the concentration of cortisol in the inner zone decreased by only one third, while the concentration of progesterone did not change. These results in association with previous reports indicate that the zona reticularis of the guinea pig adrenal cortex (in contrast to the zona fasciculata) is not regulated by ACTH in terms of either steroidogenesis or maintenance of cell growth.

Functional differences in cholesterol ester hydrolase and acyl-coenzyme-A/cholesterol acyltransferase between the outer and inner zones of the guinea pig adrenal cortex.

Previous studies clearly demonstrated that cells isolated from the chromatically distinct inner (primarily zona reticularis) and outer (zona fasciculata and zona glomerulosa) zones of the guinea pig adrenal cortex have vastly different steroidogenic capabilities; the outer zone produces far more cortisol than the inner zone, and mitochondrial cholesterol side-chain cleavage activity in the inner zone is not modulated by ACTH. Thus, in this study we have investigated the characteristics and properties of cholesterol ester hydrolase (CEHase) and acyl-coenzyme-A/cholesterol acyltransferase (ACAT) in the outer and inner zones of the guinea pig adrenal to clarify the zonal difference in cholesterol metabolism. CEHase showed two pH optima at around pH 4.5 and pH 7.5 in the outer zone, while optimum activity in the inner zone was found only around pH 4.5, suggesting a lack of neutral CEHase in the inner zone. The acid CEHase was found mainly in the lysosomal fraction, and the neutral CEHase was located mainly in the microsomal fraction. The neutral CEHase activity in the outer zone was significantly enhanced by ether stress, while the acid CEHase activity was not changed in either of the two zones by stress. The basal activity of ACAT was significantly higher in the outer zone than in the inner zone. The present experiments also demonstrated that the inner zone always showed lower ACAT activity than the outer zone even when added cholesterol exogenously. It is suggested that the relatively low activity of ACAT may not always be explained by the reduced content of cholesterol in the microsomal fraction of zona reticularis. ACAT activity in the outer zone was significantly decreased by ether-induced stress, but that in the inner zone was not changed. The content of esterified cholesterol in whole homogenate and the microsomal fraction was significantly decreased in the outer zone, but not in the inner zone, by ether stress. Thus, the decrease in esterified cholesterol after ether stress seems to relate to increased neutral CEHase activity and decreased ACAT activity in the outer zone. The present observation clearly indicates that the lack of neutral CEHase and the lesser activity of ACAT in the inner zone than in the outer zone may contribute to the impaired cholesterol metabolism in the inner zone.

Studies on cholesterol esterase in the rat adrenal.

We have investigated the characteristics and properties of cholesterol esterase (CEase) in the rat adrenal to clarify the mechanism of synthesis of free cholesterol from esterified cholesterol. CEase activity was estimated using substrate vesicles which were sonicated mixtures of cholesteryl oleate and phosphatidylcholine (PC). CEase showed two optima at around pH 4.5 and pH 8.25. The acid CEase was found mainly in the lysosomal fraction, and the alkaline CEase was found mainly in the microsomal fraction. Both acid and alkaline CEase activities were markedly enhanced by increasing the concentration of PC, but not by phospholipids. The activities were not increased by the addition of cAMP, ATP, and MgCl2, when the molar ratio of cholesteryl oleate to PC was 1:0.2, but were increased when the molar ratio was 1:2. Thus, it is suggested that free cholesterol for steroidogenesis may be supplied by two different organelles (lysosome and microsome), and that the composition of the substrate complex, such as the ratio of esterified cholesterol to phospholipids, may play a crucial role in the regulation of adrenal CEase. Increases in both acid and alkaline CEase activities were observed in adrenal homogenates prepared from hypophysectomized rats treated with an iv injection of ACTH when the molar ratio of cholesteryl oleate to PC used as a substrate vesicle was 1:0.2, but not when the ratio was 1:2. Therefore, the present observation indicate that activation of CEase by ACTH is dependent on the substrate state, especially that of the cholesterol ester droplet in vivo.

Regulation of cholesterol metabolism in rat adrenal glands: effect of adrenocorticotropin, cholesterol, and corticosteroids on acyl-coenzyme A synthetase and cholesterol ester hydrolases.

The regulation of cholesterol metabolism in rat adrenal glands, especially the effect of ACTH, cholesterol, and corticosteroids on acyl-coenzyme A (CoA) synthetase and cholesterol ester hydrolases was investigated. A significant increase in acyl-CoA synthetase activity and decrease in cholesterol ester hydrolase activities were observed in 24-h hypophysectomized rats. Acute injection of ACTH, however, reversed these changes, whereas dexamethasone administration had no effect. When 4-aminopyrazolo[3,4-d]pyrimidine was given to rats, adrenal cholesterol ester content and the acyl-CoA synthetase activity declined and the activities of the cholesterol ester hydrolases were increased in association with the rise of plasma ACTH concentration. When dexamethasone, which suppresses ACTH secretion, was simultaneously administered with 4-aminopyrazolo[3,4-d]pyrimidine no changes except for a decrease in plasma cholesterol level occurred. In hyperlipidemic rats the acyl-CoA synthetase activity increased when a high cholesterol diet was given and the plasma cholesterol level was increased. These results suggest that acyl-CoA synthetase is under the influence of ACTH and also the plasma cholesterol concentration, and that cholesterol ester hydrolases are mainly regulated by ACTH.

Multiplicity of the DNA-binding protein HBP-1 specific to the conserved hexameric sequence ACGTCA in various plant gene promoters.

A novel DNA-binding protein that specifically interacts with the hexameric sequence ACGTCA in the regulatory region of the wheat histone H3 gene has been identified in wheat nuclear extract and designated HBP-1a. The nuclear protein HBP-1 previously identified as a DNA-binding protein that interacts with hexameric sequences in the H3, cauliflower mosaic virus (CaMV) 35 S RNA, and nopaline synthase (NOS) promoter regions therefore has been renamed HBP-1b. The flanking sequences that surround the hexameric sequence may account for the difference in the binding properties of HBP-1a and HBP-1b.