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Query: UMLS:C0265264 (HOS)
1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plant responses to cold stress are mediated by a transcriptional cascade, in which the transcription factor ICE1 and possibly related proteins activate the expression of C-repeat (CRT)-binding factors (CBFs), leading to the transcription of downstream effector genes. The variant RING finger protein high expression of osmotically responsive gene (HOS)1 was identified genetically as a negative regulator of cold responses. We present evidence here that HOS1 is an E3 ligase required for the ubiquitination of ICE1. HOS1 physically interacts with ICE1 and mediates the ubiquitination of ICE1 both in vitro and in vivo. We found that cold induces the degradation of ICE1 in plants, and this degradation requires HOS1. Consistent with enhanced cold-responsive gene expression in loss-of-function hos1 mutant plants, overexpression of HOS1 represses the expression of CBFs and their downstream genes and confers increased sensitivity to freezing stress. Our results indicate that cold stress responses in Arabidopsis are attenuated by a ubiquitination/proteasome pathway in which HOS1 mediates the degradation of the ICE1 protein.
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PMID:The negative regulator of plant cold responses, HOS1, is a RING E3 ligase that mediates the ubiquitination and degradation of ICE1. 1670 57

Tbx5 is essential for initiation of the forelimb, and its deletion in mice results in the failure of forelimb formation. Misexpression of dominant-negative forms of Tbx5 results in limb truncations, suggesting Tbx5 is also required for forelimb outgrowth. Here we show that Tbx5 is expressed throughout the limb mesenchyme in progenitors of cartilage, tendon and muscle. Using a tamoxifeninducible Cre transgenic line, we map the time frame during which Tbx5 is required for limb development. We show that deletion of Tbx5 subsequent to limb initiation does not impair limb outgrowth. Furthermore, we distinguish two distinct phases of limb development: a Tbx5-dependent limb initiation phase, followed by a Tbx5-independent limb outgrowth phase. In humans, mutations in the T-box transcription factor TBX5 are associated with the dominant disorder Holt-Oram syndrome (HOS), which is characterised by malformations in the forelimb and heart. Our results demonstrate a short temporal requirement for Tbx5 during early limb development, and suggest that the defects found in HOS arise as a result of disrupted TBX5 function during this narrow time window.
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PMID:Tbx5 is dispensable for forelimb outgrowth. 1713 67

Holt-Oram syndrome (MIM #142900) is an autosomal-dominant disorder characterized by radial ray deformities of the upper limb associated with cardiac septation and/or conduction defects. The disorder is caused by mutations in the transcription factor TBX5. Several studies report a rather low detection rate (range, 22-35%) of TBX5 mutations in patients with a clinical suspicion of Holt-Oram syndrome. The low detection rate is attributed to clinical misdiagnosis and genetic heterogeneity. However, a detection rate up to 74% has been reported when strict inclusion criteria for Holt-Oram syndrome are applied before genetic testing. We performed mutational analysis in a cohort of 27 unrelated patients referred with a clinical diagnosis of Holt-Oram syndrome. Seven TBX5 mutations were detected by direct sequencing. The detection rate of TBX5 mutations in this co hort of patients was 25.9% but increased to 54% when the strict phenotypical criteria were applied. No mutations were found in patients who did not meet these strict phenotypical criteria. Interestingly, we were unable to identify a TBX5 mutation in six of 13 patients who did meet the strict criteria. This study confirms TBX5 genetic testing should be reserved for patients who fulfill the strict phenotypic criteria for Holt-Oram syndrome.
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PMID:Novel TBX5 mutations in patients with Holt-Oram syndrome. 1753 87

The understanding of the etiology of congenital heart disease is rapidly progressing from the recognition of embryologic origins to insight into the genetic basis for these disorders. Better understanding of the clinical implications of specific mutations should allow not only for more sensitive and specific diagnoses to be made but also for improvements in therapeutics options an efficacy. Mutations in the T-box transcription factor TBX5 cause Holt-Oram syndrome, an autosomal-dominant condition characterized by a familial history of congenital heart disease and upper limb defects. This review summarizes recent developments in the study of Holt-Oram Syndrome.
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PMID:[Genetic and congenital heart defects]. 1893 99

Epigenetic mechanisms regulate the expression of virulence traits in diverse pathogens, including protozoan and fungi. In the human fungal pathogen Candida albicans, virulence traits such as antifungal resistance, white-opaque switching, and adhesion to lung cells are regulated by histone deacetylases (HDACs). However, the role of HDACs in the regulation of the yeast-hyphal morphogenetic transitions, a critical virulence attribute of C. albicans, remains poorly explored. In this study, we wished to determine the relevance of other HDACs on C. albicans morphogenesis. We generated mutants in the HDACs HOS1, HOS2, RPD31, and HDA1 and determined their ability to filament in response to different environmental stimuli. We found that while HOS1 and RPD31 have no or a more limited role in morphogenesis, the HDACs HOS2 and HDA1 have opposite roles in the regulation of hyphal formation. Our results demonstrate an important role for HDACs on the regulation of yeast-hyphal transitions in the human pathogen C. albicans.
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PMID:HOS2 and HDA1 encode histone deacetylases with opposing roles in Candida albicans morphogenesis. 2073 94

Plants under low temperature (LT) stress exhibit a C-repeat binding factor (CBF)-dependent responsive pathway. The transcription factors in the CBF family, existing in multiple plant species, are the key regulators of the cold-responsive (COR) genes. CBF1 and CBF3 are regulated in a different way from CBF2, and CBF4 is the only known CBF gene definitely involved in abscisic acid (ABA)-dependent signaling pathways. RAP2.1 and RAP2.6 are the downstream regulators under CBFs. The upstream regulators of the CBF named inducer of CBF expression (ICE) acts as a positive regulator of CBFs. Meanwhile, these CBF signaling pathway components could associate with many other transcription activators and repressors in regulating gene expression when plants are under LT stress. HOS1 negatively regulates ICE1, which down regulates MYB15, an upstream repressor of CBFs. ZAT12 participates in the repression of CBFs, while ZAT10 and FRY2 negatively regulate the CBF-target genes. ADF5 was recently also found to repress CBFs. LOS2 works against ZAT10, and LOS4 positively regulates CBFs. SFR6 is involved in the modification of CBFs to activate the COR genes, and SIZ1-dependent sumoylation plays a positive role in the regulation of ICE1. The utilization of CBF-dependent signaling components has a broad perspective in the field of plant breeding for enhancing crop LT tolerance.
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PMID:CBF-dependent signaling pathway: a key responder to low temperature stress in plants. 2091 19

ICE1, a MYC-type transcription factor, has an important role in the induction of CBF3/DREB1A for regulation of cold signaling and tolerance. Here we reveal that serine 403 of ICE1 is involved in regulating the transactivation and stability of the ICE1 protein. Substitution of serine 403 by alanine enhanced the transactivational activity of ICE1 in Arabidopsis protoplasts. Over-expression of ICE1(S403A) conferred more freezing tolerance than ICE1(WT) in Arabidopsis, and the expression of cold-regulated genes such as CBF3/DREB1A, COR47 and KIN1 was enhanced in plants over-expressing ICE1(S403A). Furthermore, the ICE1(S403A) protein level was not changed after cold treatment, whereas the ICE1(WT) protein level was reduced. Interestingly, polyubiquitylation of the ICE1(S403A) protein in vivo was apparently blocked. These results demonstrate that serine 403 of ICE1 has roles in both transactivation and cold-induced degradation of ICE1 via the ubiquitin/26S proteasome pathway, suggesting that serine 403 is a key residue for the attenuation of cold-stress responses by HOS1-mediated degradation of ICE1.
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PMID:ICE1 Ser403 is necessary for protein stabilization and regulation of cold signaling and tolerance. 2144 70

Small molecules that exhibit biological activity have contributed to the understanding of the molecular mechanisms of various biological phenomena. 5-Bromodeoxyuridine (BrdU) is a thymidine analogue that modulates various biological phenomena such as cellular differentiation and cellular senescence in cultured mammalian cells. Although BrdU is thought to function through changing chromatin structure and gene expression, its precise molecular mechanisms are not understood. To study the molecular mechanism for the action of BrdU, we have employed the yeast Saccharomyces cerevisiae as a model system, and screened multi-copy suppressor genes that confer resistance to BrdU. Our genetic screen has revealed that expression of the N-terminal short fragment of TUP1, and also disruption of HDA1 or HOS1, histone deacetylases that interact with TUP1, conferred resistance to BrdU. These results suggest the implication of the chromatin proteins in the function of BrdU, and would provide novel clues to answer the old question of how BrdU modulates various biological phenomena.
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PMID:N-terminal short fragment of TUP1 confers resistance to 5-bromodeoxyuridine in the yeast Saccharomyces cerevisiae. 2171 29

Tissue anoxia is the main mechanism of the shock reaction. Here, the effect of hyperoxygenated solution (HOS) on acute haemorrhagic shock was studied in rabbits. At 60 min after shock, rabbits were infused intravenously with hyperoxygenated solution at 10 (HOS1 group) or 20 ml/kg (HOS2 group) or with Ringer's solution at 10 ml/kg (RS group). Compared with values before shock, values after shock were lower for mean arterial pressure (MAP), more negative for base excess (BE) and higher for blood lactate (BL) and blood viscosity. After infusion, MAP declined more slowly in the HOS1 and HOS2 groups than in the RS group. At 30 and 60 min after infusion, arterial partial pressure of oxygen (PaO(2)) and oxygen saturation (SaO(2)) were higher and BE was less negative in the HOS1 and HOS2 groups than in the RS group, BL was lower in the HOS1 and HOS2 groups than in the RS group, and PaO(2) and SaO(2) were higher in the HOS2 group than in the HOS1 group. It was concluded that HOS infusion can rectify changes in vital signs more effectively than Ringer's solution after acute haemorrhagic shock in rabbits.
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PMID:Therapeutic effects of intravenous infusion of hyperoxygenated solution on acute haemorrhagic shock in rabbits. 2211 85

Cold stress is a major environmental factor that limits plant growth and development. The C-repeat-binding factor (CBF)-dependent cold signaling pathway is extensively studied in Arabidopsis; however, the specific protein kinases involved in this pathway remain elusive. Here we report that OST1 (open stomata 1), a well-known Ser/Thr protein kinase in ABA signaling, acts upstream of CBFs to positively regulate freezing tolerance. The ost1 mutants show freezing hypersensitivity, whereas transgenic plants overexpressing OST1 exhibit enhanced freezing tolerance. The OST1 kinase is activated by cold stress. Moreover, OST1 interacts with both the transcription factor ICE1 and the E3 ligase HOS1 in the CBF pathway. Cold-activated OST1 phosphorylates ICE1 and enhances its stability and transcriptional activity. Meanwhile, OST1 interferes with the interaction between HOS1 and ICE1, thus suppressing HOS1-mediated ICE1 degradation under cold stress. Our results thus uncover the unexpected roles of OST1 in modulating CBF-dependent cold signaling in Arabidopsis.
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PMID:OST1 kinase modulates freezing tolerance by enhancing ICE1 stability in Arabidopsis. 2568 Aug 56


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