scholarly journals A dominant-negative form of the E3 ubiquitin ligase Cullin-1 disrupts the correct allocation of cell fate in the neural crest lineage

Development ◽  
2006 ◽  
Vol 133 (3) ◽  
pp. 559-568 ◽  
Author(s):  
J. Voigt
Keyword(s):  
Neural Crest ◽  
Cell Fate ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Dominant Negative ◽  
Dominant Negative Form ◽  
Negative Form

Chimeric Leukemic Protein PLZF/RARα Functions as an Adoptor for Cul3-Based E3 Ubiquitin Ligase To Regulate Proteosomal Degradation of RXRα.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1926-1926
Author(s):  
Masahiro Onozawa ◽  
Takeshi Kondo ◽  
Hiroe Kanamori ◽  
Kaoru Kahata ◽  
Satoshi Hashino ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Chromosomal Translocation ◽  
Dominant Negative ◽  
Luciferase Assay ◽  
The Novel ◽  
All Trans Retinoic Acid ◽  
Dominant Negative Form ◽  
Negative Form

Abstract Typical acute promyelocytic leukemia (APL) is associated with expression of the PML/RARα fusion protein resulting from chromosomal translocation t(15;17) and responsiveness to treatment with all-trans retinoic acid (ATRA). A few population of APL is associated with variant chromosomal translocations, t(11;17), t(5;17) and t(17;17). PLZF/RARα is the chimeric fusion protein resulting from the chromosomal translocation, t(11;17)(q23;q21). APL cells with PLZF/RARα have been reported to be unresponsive to ATRA-induced terminal differentiation clinically and experimentally. The molecular basis of unresponsiveness in PLZF/RARα-derived APL cells against ATRA explained by a rigid interaction between BTB/POZ domain of PLZF and a transcriptional co-repressor, N-CoR. PLZF/RARα contains BTB/POZ domain in its N-terminus. BTB/POZ domain is developmentally conserved among various species, and recently several BTB/POZ-containing molecules have been reported to function as substrate-specific adaptors for Cul3-based E3 ubiquitin ligase. Here we examined the possibility that PLZF/RARα functions as an E3 ligase. We performed the series of transient transfection analysis. By immunoprecipitation assay, PLZF/RARα associated with Cul3, and PLZF/RARα also associated with RXRα. PLZF/RARα accelerated an ubiquitin-dependent degradation of RXRα, and resulted in the decreased expression of RXRα. This degradation of RXRα was dependent on the expression level of PLZF/RARα. On the contrary, co-expression of dominant negative form of Cul3 with PLZF/RARα resulted in the restored expression of RXRα. When we expressed PML/RARα, PLZF or PLZF/RARαΔBTB, the accelerated degradation of RXRα was not observed. In RARα-responsive luciferase assay, PLZF/RARα repressed ATRA response. Consistent with the result that PLZF/RARαΔBTB did not down-regulate the expression of RXRα, PLZF/RARαΔBTB did not repress ATRA response. In addition, the transduction of recombinant RXRα molecule into PLZF/RARα expressing cells partially restored ATRA-responsiveness. Collectively, we suggest that ATRA resistance in PLZF/RARα-positive cells is explained by the novel function of PLZF/RARα molecule.

Requirement ofFoxD3-class signaling for neural crest determination inXenopus

Development ◽  
2001 ◽  
Vol 128 (13) ◽  
pp. 2525-2536 ◽  
Author(s):  
Noriaki Sasai ◽  
Kenji Mizuseki ◽  
Yoshiki Sasai
Keyword(s):  
Neural Crest ◽  
Dominant Negative ◽  
Related Factor ◽  
Embryonic Patterning ◽  
Loss Of Function ◽  
Upstream Regulator ◽  
Dominant Negative Form ◽  
Neural Crest Differentiation ◽  
Negative Form

Fox factors (winged-helix transcription factors) play important roles in early embryonic patterning. We show here that FoxD3 (Forkhead 6) regulates neural crest determination in Xenopus embryos. Expression of FoxD3 in the presumptive neural crest region starts at the late gastrula stage in a manner similar to that of Slug, and overlaps with that of Zic-r1. When overexpressed in the embryo and in ectodermal explants, FoxD3 induces expression of neural crest markers. Attenuation of FoxD3-related signaling by a dominant-negative FoxD3 construct (FoxD3delN) inhibits neural crest differentiation in vivo without suppressing the CNS marker Sox2. Interestingly, these loss-of-function phenotypes are reversed by coinjecting Slug. In animal cap explants, neural crest differentiation induced by Slug and Wnt3a is also inhibited by FoxD3delN but not by a dominant-negative form of XBF2. Loss-of-function studies using dominant-negative forms of FoxD3 and Slug indicate that Slug induction by Zic factors requires FoxD3-related signaling, and that FoxD3 and Slug have different requirements in inducing downstream neural crest markers. These data demonstrate that FoxD3 (or its closely related factor) is an essential upstream regulator of neural crest determination.

scholarly journals Unique functions for Notch4 in murine embryonic lymphangiogenesis

Angiogenesis ◽  
2021 ◽  
Author(s):  
Ajit Muley ◽  
Minji Kim Uh ◽  
Glicella Salazar-De Simone ◽  
Bhairavi Swaminathan ◽  
Jennifer M. James ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Dominant Role ◽  
Dominant Negative ◽  
Cell Fate Decisions ◽  
Dominant Negative Form ◽  
Evolutionarily Conserved ◽  
Lymphatic Development ◽  
Lymphatic Density ◽  
Negative Form

AbstractIn mice, embryonic dermal lymphatic development is well understood and used to study gene functions in lymphangiogenesis. Notch signaling is an evolutionarily conserved pathway that modulates cell fate decisions, which has been shown to both inhibit and promote dermal lymphangiogenesis. Here, we demonstrate distinct roles for Notch4 signaling versus canonical Notch signaling in embryonic dermal lymphangiogenesis. Actively growing embryonic dermal lymphatics expressed NOTCH1, NOTCH4, and DLL4 which correlated with Notch activity. In lymphatic endothelial cells (LECs), DLL4 activation of Notch induced a subset of Notch effectors and lymphatic genes, which were distinctly regulated by Notch1 and Notch4 activation. Treatment of LECs with VEGF-A or VEGF-C upregulated Dll4 transcripts and differentially and temporally regulated the expression of Notch1 and Hes/Hey genes. Mice nullizygous for Notch4 had an increase in the closure of the lymphangiogenic fronts which correlated with reduced vessel caliber in the maturing lymphatic plexus at E14.5 and reduced branching at E16.5. Activation of Notch4 suppressed LEC migration in a wounding assay significantly more than Notch1, suggesting a dominant role for Notch4 in regulating LEC migration. Unlike Notch4 nulls, inhibition of canonical Notch signaling by expressing a dominant negative form of MAML1 (DNMAML) in Prox1+ LECs led to increased lymphatic density consistent with an increase in LEC proliferation, described for the loss of LEC Notch1. Moreover, loss of Notch4 did not affect LEC canonical Notch signaling. Thus, we propose that Notch4 signaling and canonical Notch signaling have distinct functions in the coordination of embryonic dermal lymphangiogenesis.

scholarly journals Modulation of flight and feeding behaviours requires presynaptic IP3Rs in dopaminergic neurons

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Anamika Sharma ◽  
Gaiti Hasan
Keyword(s):  
Dopaminergic Neurons ◽  
Calcium Release ◽  
Neural Circuit ◽  
Dominant Negative ◽  
Neuronal Function ◽  
Axonal Projections ◽  
Dominant Negative Form ◽  
Internal States ◽  
Innate Behaviour ◽  
Negative Form

Innate behaviours, although robust and hard wired, rely on modulation of neuronal circuits, for eliciting an appropriate response according to internal states and external cues. Drosophila flight is one such innate behaviour that is modulated by intracellular calcium release through inositol 1,4,5-trisphosphate receptors (IP3Rs). Cellular mechanism(s) by which IP3Rs modulate neuronal function for specific behaviours remain speculative, in vertebrates and invertebrates. To address this, we generated an inducible dominant negative form of the IP3R (IP3RDN). Flies with neuronal expression of IP3RDN exhibit flight deficits. Expression of IP3RDN helped identify key flight-modulating dopaminergic neurons with axonal projections in the mushroom body. Flies with attenuated IP3Rs in these presynaptic dopaminergic neurons exhibit shortened flight bouts and a disinterest in seeking food, accompanied by reduced excitability and dopamine release upon cholinergic stimulation. Our findings suggest that the same neural circuit modulates the drive for food search and for undertaking longer flight bouts.

scholarly journals Suppression of thymic development by the dominant-negative form of Gads

2001 ◽  
Vol 13 (6) ◽  
pp. 777-783 ◽  
Author(s):  
Kazu Kikuchi ◽  
Yoshitada Kawasaki ◽  
Naoto Ishii ◽  
Yoshiteru Sasaki ◽  
Hironobu Asao ◽  
...  
Keyword(s):  
Dominant Negative ◽  
Thymic Development ◽  
Dominant Negative Form ◽  
Negative Form
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