scholarly journals Direct photoresponsive inhibition of a p53-like transcription activation domain in PIF3 by Arabidopsis phytochrome B

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chan Yul Yoo ◽  
Jiangman He ◽  
Qing Sang ◽  
Yongjian Qiu ◽  
Lingyun Long ◽  
...  
Keyword(s):  
Target Genes ◽  
Transcription Activation ◽  
Phytochrome B ◽  
Activation Domain ◽  
Signaling Mechanism ◽  
Transactivation Activity ◽  
Transcription Activation Domain ◽  
Signaling Mechanisms ◽  
The Stability

AbstractPhotoactivated phytochrome B (PHYB) binds to antagonistically acting PHYTOCHROME-INTERACTING transcription FACTORs (PIFs) to regulate hundreds of light responsive genes in Arabidopsis by promoting PIF degradation. However, whether PHYB directly controls the transactivation activity of PIFs remains ambiguous. Here we show that the prototypic PIF, PIF3, possesses a p53-like transcription activation domain (AD) consisting of a hydrophobic activator motif flanked by acidic residues. A PIF3mAD mutant, in which the activator motif is replaced with alanines, fails to activate PIF3 target genes in Arabidopsis, validating the functions of the PIF3 AD in vivo. Intriguingly, the N-terminal photosensory module of PHYB binds immediately adjacent to the PIF3 AD to repress PIF3’s transactivation activity, demonstrating a novel PHYB signaling mechanism through direct interference of the transactivation activity of PIF3. Our findings indicate that PHYB, likely also PHYA, controls the stability and activity of PIFs via structurally separable dual signaling mechanisms.

scholarly journals Direct photoresponsive inhibition of a p53-like transcription activation domain in PIF3 by Arabidopsis phytochrome B

2021 ◽  
Author(s):  
Chan Yul Yoo ◽  
Qing Sang ◽  
Jiangman He ◽  
Yongjian Qiu ◽  
Lingyun Long ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Target Genes ◽  
Transcription Activation ◽  
Phytochrome B ◽  
Activation Domain ◽  
Light Responses ◽  
Dark Light ◽  
Transactivation Activity ◽  
Transcription Activation Domain

Phytochrome B (PHYB) triggers diverse light responses in Arabidopsis by binding to a group of antagonistically acting PHYTOCHROME-INTERACTING transcription FACTORs (PIFs) to promote PIF degradation, consequently downregulating PIF target genes. However, whether PHYB directly controls the transactivation activity of PIFs remains ambiguous. Here we show that the prototypic PIF, PIF3, possesses a p53-like transcription activation domain (TAD) consisting of a sequence-specific, hydrophobic activator motif surrounded by acidic residues. A PIF3mTAD mutant in which the activator motif is replaced with alanines fails to activate PIF3 target genes in Arabidopsis in dark, light, and shade conditions, validating the in vivo functions of the PIF3 TAD. Intriguingly, binding of the N-terminal photosensory module of PHYB to the PHYB-binding site adjacent to the TAD inhibits its transactivation activity. These results unveil a photoresponsive transcriptional switching mechanism in which photoactivated PHYB directly masks the transactivation activity of PIF3. Our study also suggests the unexpected conservation of sequence-specific TADs between the animal and plant kingdoms.

scholarly journals Targeting the TR4 nuclear receptor-mediated lncTASR/AXL signaling with tretinoin increases the sunitinib sensitivity to better suppress the RCC progression

Oncogene ◽  
2019 ◽  
Vol 39 (3) ◽  
pp. 530-545 ◽  
Author(s):  
Hangchuan Shi ◽  
Yin Sun ◽  
Miao He ◽  
Xiong Yang ◽  
Michiaki Hamada ◽  
...  
Keyword(s):  
Small Molecules ◽  
Nuclear Receptor ◽  
Preclinical Study ◽  
First Line ◽  
Novel Therapy ◽  
Signaling Mechanism ◽  
First Line Therapy ◽  
Line Therapy ◽  
The Stability

Abstract Renal cell carcinoma (RCC) is one of the most lethal urological tumors. Using sunitinib to improve the survival has become the first-line therapy for metastatic RCC patients. However, the occurrence of sunitinib resistance in the clinical application has curtailed its efficacy. Here we found TR4 nuclear receptor might alter the sunitinib resistance to RCC via altering the TR4/lncTASR/AXL signaling. Mechanism dissection revealed that TR4 could modulate lncTASR (ENST00000600671.1) expression via transcriptional regulation, which might then increase AXL protein expression via enhancing the stability of AXL mRNA to increase the sunitinib resistance in RCC. Human clinical surveys also linked the expression of TR4, lncTASR, and AXL to the RCC survival, and results from multiple RCC cell lines revealed that targeting this newly identified TR4-mediated signaling with small molecules, including tretinoin, metformin, or TR4-shRNAs, all led to increase the sunitinib sensitivity to better suppress the RCC progression, and our preclinical study using the in vivo mouse model further proved tretinoin had a better synergistic effect to increase sunitinib sensitivity to suppress RCC progression. Future successful clinical trials may help in the development of a novel therapy to better suppress the RCC progression.

Identification of Novel and Cell Type Enriched Cofactors of the Transcription Activation Domain of RelA (p65 NF-κB)

2005 ◽  
Vol 4 (4) ◽  
pp. 1381-1390 ◽  
Author(s):  
Heather R. Owen ◽  
Manfredo Quadroni ◽  
Willy Bienvenut ◽  
Christine Buerki ◽  
Michael O. Hottiger
Keyword(s):  
Transcription Activation ◽  
Cell Type ◽  
Activation Domain ◽  
Transcription Activation Domain

scholarly journals A tryptophan-rich peptide acts as a transcription activation domain

2010 ◽  
Vol 11 (1) ◽  
Author(s):  
Chen-Huan Lin ◽  
Grace Lin ◽  
Chia-Pei Chang ◽  
Chien-Chia Wang
Keyword(s):  
Transcription Activation ◽  
Activation Domain ◽  
Transcription Activation Domain

scholarly journals Multiple layers of regulation of human heat shock transcription factor 1.

1995 ◽  
Vol 15 (8) ◽  
pp. 4319-4330 ◽  
Author(s):  
J Zuo ◽  
D Rungger ◽  
R Voellmy
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Dna Binding ◽  
Cell Activation ◽  
Transcription Activation ◽  
Heat Shock Transcription Factor ◽  
Activation Domain ◽  
Sequence Element ◽  
Transcription Activation Domain ◽  
Transcription Factor 1

Upon heat stress, monomeric human heat shock transcription factor 1 (hHSF1) is converted to a trimer, acquires DNA-binding ability, is transported to the nucleus, and becomes transcriptionally competent. It was not known previously whether these regulatory changes are caused by a single activation event or whether they occur independently from one another, providing a multilayered control that may prevent inadvertant activation of hHSF1. Comparison of wild-type and mutant hHSF1 expressed in Xenopus oocytes and human HeLa cells suggested that retention of hHSF1 in the monomeric form depends on hydrophobic repeats (LZ1 to LZ3) and a carboxy-terminal sequence element in hHSF1 as well as on the presence of a titratable factor in the cell. Oligomerization of hHSF1 appears to induce DNA-binding activity as well as to uncover an amino-terminally located nuclear localization signal. A mechanism distinct from that controlling oligomerization regulates the transcriptional competence of hHSF1. Components of this mechanism were mapped to a region, including LZ2 and nearby sequences downstream from LZ2, that is clearly separated from the carboxy-terminally located transcription activation domain(s). We propose the existence of a fold-back structure that masks the transcription activation domain in the unstressed cell but is opened up by modification of hHSF1 and/or binding of a factor facilitating hHSF1 unfolding in the stressed cell. Activation of hHSF1 appears to involve at least two independently regulated structural transitions.

Oncogenic transformation by vrel requires an amino-terminal activation domain

1990 ◽  
Vol 10 (6) ◽  
pp. 2840-2847
Author(s):  
J Kamens ◽  
P Richardson ◽  
G Mosialos ◽  
R Brent ◽  
T Gilmore
Keyword(s):  
Target Genes ◽  
Transcription Activation ◽  
Oncogenic Transformation ◽  
Activation Domain ◽  
Amino Terminal ◽  
Region I ◽  
Mutant Derivative ◽  
Dorsal Gene ◽  
Region Ii ◽  
Acidic Region

The mechanism by which the products of the v-rel oncogene, the corresponding c-rel proto-oncogene, and the related dorsal gene of Drosophila melanogaster exert their effects is not clear. Here we show that the v-rel, chicken c-rel, and dorsal proteins activated gene expression when fused to LexA sequences and bound to DNA upstream of target genes in Saccharomyces cerevisiae. We have defined two distinct activation regions in the c-rel protein. Region I, located in the amino-terminal half of rel and dorsal proteins, contains no stretches of glutamines, prolines, or acidic amino acids and therefore may be a novel activation domain. Lesions in the v-rel protein that diminished or abolished oncogenic transformation of avian spleen cells correspondingly affected transcription activation by region I. Region II, located in the carboxy terminus of the c-rel protein, is highly acidic. Region II is not present in the v-rel protein or in a transforming mutant derivative of the c-rel protein. Our results show that the oncogenicity of Rel proteins requires activation region I and suggest that the biological function of rel and dorsal proteins depends on transcription activation by this region.

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