scholarly journals A novel Xenopus Smad-interacting forkhead transcription factor (XFast-3) cooperates with XFast-1 in regulating gastrulation movements

Development ◽  
2002 ◽  
Vol 129 (12) ◽  
pp. 2823-2834 ◽  
Author(s):  
Michael Howell ◽  
Gareth J. Inman ◽  
Caroline S. Hill

In early Xenopus embryos, the prototypical XFast-1/Smad2/Smad4 complex ARF1 is induced at the Mix.2 ARE by activin overexpression. We have characterised ARF2, a related, but much more abundant, complex formed during gastrulation in response to endogenous TGFβ family members and we have identified a novel Fast family member, XFast-3, as its transcription factor component. Endogenous ARF2 efficiently competes out ARF1 at early gastrulation, due to the ability of XFast-3 to interact with activated Smads with much higher affinity than XFast-1. We demonstrate that ARF1 and ARF2 are activated by distinct TGFβ family members. Using morpholino antisense oligonucleotides to deplete levels of the constituent transcription factors XFast-1 and XFast-3 specifically, we demonstrate an important role for ARF1 and ARF2 in early Xenopus embryos in controlling the convergent extension movements of gastrulation.

2017 ◽  
Vol 114 (45) ◽  
pp. E9722-E9729 ◽  
Author(s):  
Ying-Chung Jimmy Lin ◽  
Hao Chen ◽  
Quanzi Li ◽  
Wei Li ◽  
Jack P. Wang ◽  
...  

Secondary cell wall (SCW) biosynthesis is the biological process that generates wood, an important renewable feedstock for materials and energy. NAC domain transcription factors, particularly Vascular-Related NAC-Domain (VND) and Secondary Wall-Associated NAC Domain (SND) proteins, are known to regulate SCW differentiation. The regulation of VND and SND is important to maintain homeostasis for plants to avoid abnormal growth and development. We previously identified a splice variant, PtrSND1-A2IR, derived from PtrSND1-A2 as a dominant-negative regulator, which suppresses the transactivation of all PtrSND1 family members. PtrSND1-A2IR also suppresses the self-activation of the PtrSND1 family members except for its cognate transcription factor, PtrSND1-A2, suggesting the existence of an unknown factor needed to regulate PtrSND1-A2. Here, a splice variant, PtrVND6-C1IR, derived from PtrVND6-C1 was discovered that suppresses the protein functions of all PtrVND6 family members. PtrVND6-C1IR also suppresses the expression of all PtrSND1 members, including PtrSND1-A2, demonstrating that PtrVND6-C1IR is the previously unidentified regulator of PtrSND1-A2. We also found that PtrVND6-C1IR cannot suppress the expression of its cognate transcription factor, PtrVND6-C1. PtrVND6-C1 is suppressed by PtrSND1-A2IR. Both PtrVND6-C1IR and PtrSND1-A2IR cannot suppress their cognate transcription factors but can suppress all members of the other family. The results indicate that the splice variants from the PtrVND6 and PtrSND1 family may exert reciprocal cross-regulation for complete transcriptional regulation of these two families in wood formation. This reciprocal cross-regulation between families suggests a general mechanism among NAC domain proteins and likely other transcription factors, where intron-retained splice variants provide an additional level of regulation.


2001 ◽  
Vol 21 (3) ◽  
pp. 952-965 ◽  
Author(s):  
Anne Brunet ◽  
Jongsun Park ◽  
Hien Tran ◽  
Linda S. Hu ◽  
Brian A. Hemmings ◽  
...  

ABSTRACT Serum- and glucocorticoid-inducible kinases (SGKs) form a novel family of serine/threonine kinases that are activated in response to a variety of extracellular stimuli. SGKs are related to Akt (also called PKB), a serine/threonine kinase that plays a crucial role in promoting cell survival. Like Akt, SGKs are activated by the phosphoinositide-3 kinase (PI3K) and translocate to the nucleus upon growth factor stimulation. However the physiological substrates and cellular functions of SGKs remained to be identified. We hypothesized that SGKs regulate cellular functions in concert with Akt by phosphorylating common targets within the nucleus. The best-characterized nuclear substrates of Akt are transcription factors of the Forkhead family. Akt phosphorylates Forkhead transcription factors such as FKHRL1, leading to FKHRL1's exit from the nucleus and the consequent shutoff of FKHRL1 target genes. We show here that SGK1, like Akt, promotes cell survival and that it does so in part by phosphorylating and inactivating FKHRL1. However, SGK and Akt display differences with respect to the efficacy with which they phosphorylate the three regulatory sites on FKHRL1. While both kinases can phosphorylate Thr-32, SGK displays a marked preference for Ser-315 whereas Akt favors Ser-253. These findings suggest that SGK and Akt may coordinately regulate the function of FKHRL1 by phosphorylating this transcription factor at distinct sites. The efficient phosphorylation of these three sites on FKHRL1 by SGK and Akt appears to be critical to the ability of growth factors to suppress FKHRL1-dependent transcription, thereby preventing FKHRL1 from inducing cell cycle arrest and apoptosis. These findings indicate that SGK acts in concert with Akt to propagate the effects of PI3K activation within the nucleus and to mediate the biological outputs of PI3K signaling, including cell survival and cell cycle progression.


Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1437
Author(s):  
Gianmarco Stati ◽  
Francesca Passaretta ◽  
Florelle Gindraux ◽  
Lucia Centurione ◽  
Roberta Di Pietro

In the framework of space flight, the risk of radiation carcinogenesis is considered a “red” risk due to the high likelihood of occurrence as well as the high potential impact on the quality of life in terms of disease-free survival after space missions. The cyclic AMP response element-binding protein (CREB) is overexpressed both in haematological malignancies and solid tumours and its expression and function are modulated following irradiation. The CREB protein is a transcription factor and member of the CREB/activating transcription factor (ATF) family. As such, it has an essential role in a wide range of cell processes, including cell survival, proliferation, and differentiation. Among the CREB-related nuclear transcription factors, NF-κB and p53 have a relevant role in cell response to ionising radiation. Their expression and function can decide the fate of the cell by choosing between death or survival. The aim of this review was to define the role of the CREB/ATF family members and the related transcription factors in the response to ionising radiation of human haematological malignancies and solid tumours.


2000 ◽  
Vol 10 (19) ◽  
pp. 1201-1204 ◽  
Author(s):  
Pascale F Dijkers ◽  
Rene H Medema† ◽  
Jan-Willem J Lammers ◽  
Leo Koenderman ◽  
Paul J Coffer

2016 ◽  
Author(s):  
Jennifer Lachowiec ◽  
G. Alex Mason ◽  
Karla Schultz ◽  
Christine Queitsch

ABSTRACTOrganismal development is remarkably robust, tolerating stochastic errors to produce consistent, so-called canalized adult phenotypes. The mechanistic underpinnings of developmental robustness are poorly understood, but recent studies implicate certain features of genetic networks such as functional redundancy, connectivity, and feedback. Here, we examine the BRZ/BEH gene family, whose function is crucial for embryonic stem development in the plant Arabidopsis thaliana, to test current assumptions on functional redundancy and trait robustness. Our analyses of BRZ/BEH gene mutants and mutant combinations revealed that functional redundancy among gene family members does not contribute to trait robustness. Connectivity is another commonly cited determinant of robustness; however, we found no correlation between connectivity among gene family members or their connectivity with other transcription factors and effects on robustness. Instead, we found that only BEH4, the most ancient family member, modulated developmental robustness. We present evidence that regulatory cross-talk among gene family members is integrated by BEH4 and promotes wild-type levels of developmental robustness. Further, the chaperone HSP90, a known determinant of developmental robustness, appears to act via BEH4 in maintaining robustness of embryonic stem length. In summary, we demonstrate that even among closely related transcription factors, trait robustness can arise through the activity of a single gene family member, challenging common assumptions about the molecular underpinnings of robustness.


2018 ◽  
Vol 3 (2) ◽  
pp. 76
Author(s):  
Novi Anggun Pusvitasary

Pneumonia disease is the leading cause of death of babies in the world. The prevalence of pneumonia in infants is 18.5 / mil. Data from Samarinda City Health Office during the last 1 year there are 91 cases of pneumonia in Karang Anyar Village and 63 cases in Teluk Lerong Ulu Village. Factors causing pneumonia are toddler factors, behavioral factors, and environmental factors. The results show there is a relationship between house humidity (p value = 0,013; OR = 0,192), house dwelling density (p value = 0,024; OR = 0,214), and family member smoking behavior (p value = 0,006; OR = 10,450) with incidence of pneumonia in toddlers in the Working Area of Puskesmas Wonorejo Samarinda. There was no correlation between house temperature (p value = 0,214; OR = 0,337), house lighting (p value = 0,095; OR = 3,188) and family disease history (p value = 0,707; OR = 0,753) with Pneumonia occurrence in infant in region Work Puskesmas Wonorejo Samarinda. It was concluded that there was a relationship between house humidity, home dwelling density, and smoking behavior of family members with the incidence of pneumonia in infants. It is recommended to be able to apply housing health requirements that meet health standards to reduce the incidence of pneumonia in infants and change smoking habits.


2005 ◽  
Vol 83 (4) ◽  
pp. 535-547 ◽  
Author(s):  
Gareth N Corry ◽  
D Alan Underhill

To date, the majority of the research regarding eukaryotic transcription factors has focused on characterizing their function primarily through in vitro methods. These studies have revealed that transcription factors are essentially modular structures, containing separate regions that participate in such activities as DNA binding, protein–protein interaction, and transcriptional activation or repression. To fully comprehend the behavior of a given transcription factor, however, these domains must be analyzed in the context of the entire protein, and in certain cases the context of a multiprotein complex. Furthermore, it must be appreciated that transcription factors function in the nucleus, where they must contend with a variety of factors, including the nuclear architecture, chromatin domains, chromosome territories, and cell-cycle-associated processes. Recent examinations of transcription factors in the nucleus have clarified the behavior of these proteins in vivo and have increased our understanding of how gene expression is regulated in eukaryotes. Here, we review the current knowledge regarding sequence-specific transcription factor compartmentalization within the nucleus and discuss its impact on the regulation of such processes as activation or repression of gene expression and interaction with coregulatory factors.Key words: transcription, subnuclear localization, chromatin, gene expression, nuclear architecture.


2021 ◽  
Vol 22 (15) ◽  
pp. 8193
Author(s):  
Daniel Pérez-Cremades ◽  
Ana B. Paes ◽  
Xavier Vidal-Gómez ◽  
Ana Mompeón ◽  
Carlos Hermenegildo ◽  
...  

Background/Aims: Estrogen has been reported to have beneficial effects on vascular biology through direct actions on endothelium. Together with transcription factors, miRNAs are the major drivers of gene expression and signaling networks. The objective of this study was to identify a comprehensive regulatory network (miRNA-transcription factor-downstream genes) that controls the transcriptomic changes observed in endothelial cells exposed to estradiol. Methods: miRNA/mRNA interactions were assembled using our previous microarray data of human umbilical vein endothelial cells (HUVEC) treated with 17β-estradiol (E2) (1 nmol/L, 24 h). miRNA–mRNA pairings and their associated canonical pathways were determined using Ingenuity Pathway Analysis software. Transcription factors were identified among the miRNA-regulated genes. Transcription factor downstream target genes were predicted by consensus transcription factor binding sites in the promoter region of E2-regulated genes by using JASPAR and TRANSFAC tools in Enrichr software. Results: miRNA–target pairings were filtered by using differentially expressed miRNAs and mRNAs characterized by a regulatory relationship according to miRNA target prediction databases. The analysis identified 588 miRNA–target interactions between 102 miRNAs and 588 targets. Specifically, 63 upregulated miRNAs interacted with 295 downregulated targets, while 39 downregulated miRNAs were paired with 293 upregulated mRNA targets. Functional characterization of miRNA/mRNA association analysis highlighted hypoxia signaling, integrin, ephrin receptor signaling and regulation of actin-based motility by Rho among the canonical pathways regulated by E2 in HUVEC. Transcription factors and downstream genes analysis revealed eight networks, including those mediated by JUN and REPIN1, which are associated with cadherin binding and cell adhesion molecule binding pathways. Conclusion: This study identifies regulatory networks obtained by integrative microarray analysis and provides additional insights into the way estradiol could regulate endothelial function in human endothelial cells.


Sign in / Sign up

Export Citation Format

Share Document