Publications - Molecular Signal Processing

The transition to flowering is governed by different pathways integrating endogenous and exogenous signals. Here, we evaluated the role of the phytohormone cytokinin (CK) in regulating Arabidopsis thaliana flowering time. By analyzing key mutants in CK metabolism, transport and signalling, we found that the hormone promotes flowering under both long-day (LD) and short-day (SD) conditions, with a stronger impact on flowering under SDs. Genetic analyses indicated that both trans- and cis-zeatin regulate the floral transition, while isopentenyladenine plays a minor role. Blocking CK export from roots and reciprocal grafting experiments revealed that root-derived CK is an important flowering signal. Perception and transmission of the CK flowering signal depended on distinct CK receptors, phosphotransmitter proteins and several B-type response regulators. Further, CK functioned through floral integrators such as OVEREXPRESSION OF CONSTANS1 (SOC1) and components of the age pathway. The CK status of plants affected the levels of the age pathway microRNAs miR156 and miR172. Cytokinin-promoted flowering required the miR156-target SQUAMOSA PROMOTER BINDING PROTEIN-LIKE15 (SPL15) and miR172, and the late-flowering phenotype of LD-grown CK-deficient plants depended on miR172-targeted APETALA2 (AP2)-like genes encoding floral repressors. Collectively, this study shows that CK regulates flowering time through the two-component signaling system and components of the age pathway, providing a genetic framework for future investigations.

The transition to flowering is governed by different pathways integrating endogenous and exogenous signals. Here, we evaluated the role of the phytohormone cytokinin (CK) in regulating Arabidopsis thaliana flowering time. By analyzing key mutants in CK metabolism, transport and signalling, we found that the hormone promotes flowering under both long-day (LD) and short-day (SD) conditions, with a stronger impact on flowering under SDs. Genetic analyses indicated that both trans- and cis-zeatin regulate the floral transition, while isopentenyladenine plays a minor role. Blocking CK export from roots and reciprocal grafting experiments revealed that root-derived CK is an important flowering signal. Perception and transmission of the CK flowering signal depended on distinct CK receptors, phosphotransmitter proteins and several B-type response regulators. Further, CK functioned through floral integrators such as OVEREXPRESSION OF CONSTANS1 (SOC1) and components of the age pathway. The CK status of plants affected the levels of the age pathway microRNAs miR156 and miR172. Cytokinin-promoted flowering required the miR156-target SQUAMOSA PROMOTER BINDING PROTEIN-LIKE15 (SPL15) and miR172, and the late-flowering phenotype of LD-grown CK-deficient plants depended on miR172-targeted APETALA2 (AP2)-like genes encoding floral repressors. Collectively, this study shows that CK regulates flowering time through the two-component signaling system and components of the age pathway, providing a genetic framework for future investigations.

We conducted a study to evaluate dietary chemopreventive strategies to reduce genotoxic effects of the carcinogens 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). PhIP and IQ are heterocyclic amines (HCAs) that are found in cooked meat and may be risk factors for cancer. Typical chemoprevention studies have used carcinogen doses many thousand-fold higher than usual human daily intake. Therefore, we administered a low dose of [14C] PhIPand [3H] IQand utilized accelerator mass spectrometry to quantify PhIP adducts in the liver, colon, prostate, and blood plasma and IQadducts in the liver and blood plasma with high sensitivity. Diets supplemented with phenethylisothiocyanate (PEITC), genistein, chlorophyllin, or lycopene were evaluated for their ability to decrease adduct formation of [14C] PhIPand [3H] IQin rats. We also examined the effect of treatments on the activity of the phase II detoxification enzymes glutathione S-transferase (GST), UDP-glucuronyltransferase (UGT), phenol sulfotransferase (SULT) and quinone reductase (QR). PEITC and chlorophyllin significantly decreased PhIP-DNA adduct levels in all tissues examined, which was reflected by similar changes in PhIP binding to albumin in the blood. In contrast, genistein and lycopene tended to increase PhIP adduct levels. The treatments did not significantly alter the level of IQ-DNA or -protein adducts in the liver.With the exception of lycopene, the treatments had some effect on the activity of one or more hepatic phase II detoxification enzymes. We conclude that PEITC and chlorophyllin are protective of PhIP-induced genotoxicity after a low exposure dose of carcinogen, possibly through modification of HCA metabolism.

We conducted a study to evaluate dietary chemopreventive strategies to reduce genotoxic effects of the carcinogens 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). PhIP and IQ are heterocyclic amines (HCAs) that are found in cooked meat and may be risk factors for cancer. Typical chemoprevention studies have used carcinogen doses many thousand-fold higher than usual human daily intake. Therefore, we administered a low dose of [14C] PhIPand [3H] IQand utilized accelerator mass spectrometry to quantify PhIP adducts in the liver, colon, prostate, and blood plasma and IQadducts in the liver and blood plasma with high sensitivity. Diets supplemented with phenethylisothiocyanate (PEITC), genistein, chlorophyllin, or lycopene were evaluated for their ability to decrease adduct formation of [14C] PhIPand [3H] IQin rats. We also examined the effect of treatments on the activity of the phase II detoxification enzymes glutathione S-transferase (GST), UDP-glucuronyltransferase (UGT), phenol sulfotransferase (SULT) and quinone reductase (QR). PEITC and chlorophyllin significantly decreased PhIP-DNA adduct levels in all tissues examined, which was reflected by similar changes in PhIP binding to albumin in the blood. In contrast, genistein and lycopene tended to increase PhIP adduct levels. The treatments did not significantly alter the level of IQ-DNA or -protein adducts in the liver.With the exception of lycopene, the treatments had some effect on the activity of one or more hepatic phase II detoxification enzymes. We conclude that PEITC and chlorophyllin are protective of PhIP-induced genotoxicity after a low exposure dose of carcinogen, possibly through modification of HCA metabolism.