DNA-binding mechanism of the Hippo pathway transcription factor TEAD4

Oncogene ◽  
2017 ◽  
Vol 36 (30) ◽  
pp. 4362-4369 ◽  
Author(s):  
Z Shi ◽  
F He ◽  
M Chen ◽  
L Hua ◽  
W Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Hippo Pathway ◽  
Binding Mechanism ◽  
The Hippo Pathway

scholarly journals Transcription factor NRF2 uses the Hippo pathway effector TAZ to induce tumorigenesis in glioblastomas

Redox Biology ◽  
2020 ◽  
Vol 30 ◽  
pp. 101425 ◽  
Author(s):  
Maribel Escoll ◽  
Diego Lastra ◽  
Marta Pajares ◽  
Natalia Robledinos-Antón ◽  
Ana I. Rojo ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Hippo Pathway ◽  
The Hippo Pathway

scholarly journals Structural insights in the DNA binding mechanism of a NAC transcription factor

2011 ◽  
Vol 67 (a1) ◽  
pp. C746-C747
Author(s):  
L. Lo Leggio ◽  
D. H. Welner ◽  
S. Lindemose ◽  
A. N. Olsen ◽  
K. Skriver
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Nac Transcription Factor ◽  
Binding Mechanism ◽  
Structural Insights

scholarly journals Shavenbaby and Yorkie mediate Hippo signaling to protect adult stem cells from apoptosis

2017 ◽  
Author(s):  
Jérôme Bohère ◽  
Alexandra Mancheno-Ferris ◽  
Kohsuke Akino ◽  
Yuya Yamabe ◽  
Sachi Inagaki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Transcription Factor ◽  
Adult Stem Cells ◽  
Hippo Pathway ◽  
Inhibitor Of Apoptosis ◽  
Hippo Signaling ◽  
Polished Rice ◽  
Organ Regeneration ◽  
The Hippo Pathway

AbstractTo compensate for accumulating damages and cell death, adult homeostasis (e.g., body fluids and secretion) requires organ regeneration, operated by long-lived stem cells. How stem cells can survive throughout the animal life yet remains poorly understood. Here we show that the transcription factor Shavenbaby (Svb, OvoL in vertebrates) is expressed in renal/nephric stem cells (RNSCs) ofDrosophilaand required for their maintenance during adulthood. As recently shown in embryos, Svb function in adult RNSCs further needs a post-translational processing mediated by Polished rice (Pri) smORF peptides and impairing Svb function leads to RNSC apoptosis. We show that Svb interacts both genetically and physically with Yorkie (YAP/TAZ in vertebrates), a nuclear effector of the Hippo pathway, to activate the expression of the inhibitor of apoptosisDIAP1. These data therefore identify Svb as a novel nuclear effector in the Hippo pathway, critical for the survival of adult somatic stem cells.

scholarly journals Activation of the Hippo Pathway in Rana sylvatica: Yapping Stops in Response to Anoxia

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1422
Author(s):  
Aakriti Gupta ◽  
Kenneth B. Storey
Keyword(s):  
Dna Binding ◽  
Gene Transcription ◽  
Hippo Pathway ◽  
Rana Sylvatica ◽  
Whole Body ◽  
Nuclear Fraction ◽  
Wood Frogs ◽  
Downstream Targets ◽  
Protein Levels ◽  
The Hippo Pathway

Wood frogs (Rana sylvatica) display well-developed anoxia tolerance as one component of their capacity to endure prolonged whole-body freezing during the winter months. Under anoxic conditions, multiple cellular responses are triggered to efficiently cope with stress by suppressing gene transcription and promoting activation of mechanisms that support cell survival. Activation of the Hippo signaling pathway initiates a cascade of protein kinase reactions that end with phosphorylation of YAP protein. Multiple pathway components of the Hippo pathway were analyzed via immunoblotting, qPCR or DNA-binding ELISAs to assess the effects of 24 h anoxia and 4 h aerobic recovery, compared with controls, on liver and heart metabolism of wood frogs. Immunoblot results showed significant increases in the relative levels of multiple proteins of the Hippo pathway representing an overall activation of the pathway in both organs under anoxia stress. Upregulation of transcript levels further confirmed this. A decrease in YAP and TEAD protein levels in the nuclear fraction also indicated reduced translocation of these proteins. Decreased DNA-binding activity of TEAD at the promoter region also suggested repression of gene transcription of its downstream targets such as SOX2 and OCT4. Furthermore, changes in the protein levels of two downstream targets of TEAD, OCT4 and SOX2, established regulated transcriptional activity and could possibly be associated with the activation of the Hippo pathway. Increased levels of TAZ in anoxic hearts also suggested its involvement in the repair mechanism for damage caused to cardiac muscles during anoxia. In summary, this study provides the first insights into the role of the Hippo pathway in maintaining cellular homeostasis in response to anoxia in amphibians.

scholarly journals Parallel Activin and BMP signaling coordinates R7/R8 photoreceptor subtype pairing in the stochastic Drosophila retina

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Brent S Wells ◽  
Daniela Pistillo ◽  
Erin Barnhart ◽  
Claude Desplan
Keyword(s):  
Transcription Factor ◽  
Color Vision ◽  
Growth Regulator ◽  
Hippo Pathway ◽  
Bmp Signaling ◽  
Processing Factor ◽  
Activin Receptor ◽  
The Hippo Pathway ◽  
To Receive ◽  
Tgfβ Pathway

Drosophila color vision is achieved by comparing outputs from two types of color-sensitive photoreceptors, R7 and R8. Ommatidia (unit eyes) are classified into two subtypes, known as ‘pale’ or ‘yellow’, depending on Rhodopsin expression in R7 and R8. Subtype specification is controlled by a stochastic decision in R7 and instructed to the underlying R8. We find that the Activin receptor Baboon is required in R8 to receive non-redundant signaling from the three Activin ligands, activating the transcription factor dSmad2. Concomitantly, two BMP ligands activate their receptor, Thickveins, and the transcriptional effector, Mad. The Amon TGFβ processing factor appears to regulate components of the TGFβ pathway specifically in pale R7. Mad and dSmad2 cooperate to modulate the Hippo pathway kinase Warts and the growth regulator Melted; two opposing factors of a bi-stable loop regulating R8 Rhodopsin expression. Therefore, TGFβ and growth pathways interact in postmitotic cells to precisely coordinate cell-specific output.

scholarly journals Nerfin-1 represses transcriptional output of Hippo signaling in cell competition

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Pengfei Guo ◽  
Chang-Hyun Lee ◽  
Huiyan Lei ◽  
Yonggang Zheng ◽  
Katiuska Daniela Pulgar Prieto ◽  
...  
Keyword(s):  
Dna Binding ◽  
Hippo Pathway ◽  
Ectopic Expression ◽  
Tissue Growth ◽  
Hippo Signaling ◽  
Dependent Manner ◽  
Cell Competition ◽  
Regulatory Mode ◽  
The Hippo Pathway ◽  
Transcriptional Output

The Hippo tumor suppressor pathway regulates tissue growth in Drosophila by restricting the activity of the transcriptional coactivator Yorkie (Yki), which normally complexes with the TEF/TEAD family DNA-binding transcription factor Scalloped (Sd) to drive the expression of growth-promoting genes. Given its pivotal role as a central hub in mediating the transcriptional output of Hippo signaling, there is great interest in understanding the molecular regulation of the Sd-Yki complex. In this study, we identify Nerfin-1 as a transcriptional repressor that antagonizes the activity of the Sd-Yki complex by binding to the TEA DNA-binding domain of Sd. Consistent with its biochemical function, ectopic expression of Nerfin-1 results in tissue undergrowth in an Sd-dependent manner. Conversely, loss of Nerfin-1 enhances the ability of winner cells to eliminate loser cells in multiple scenarios of cell competition. We further show that INSM1, the mammalian ortholog of Nerfin-1, plays a conserved role in repressing the activity of the TEAD-YAP complex. These findings reveal a novel regulatory mode converging on the transcriptional output of the Hippo pathway that may be exploited for modulating the YAP oncoprotein in cancer and regenerative medicine.

scholarly journals Regulation of the Hippo Pathway Transcription Factor TEAD

2017 ◽  
Vol 42 (11) ◽  
pp. 862-872 ◽  
Author(s):  
Kimberly C. Lin ◽  
Hyun Woo Park ◽  
Kun-Liang Guan
Keyword(s):  
Transcription Factor ◽  
Hippo Pathway ◽  
The Hippo Pathway

scholarly journals The Ets Transcription Factor GABP Is a Component of the Hippo Pathway Essential for Growth and Antioxidant Defense

Cell Reports ◽  
2013 ◽  
Vol 3 (5) ◽  
pp. 1663-1677 ◽  
Author(s):  
Hongtan Wu ◽  
Yubo Xiao ◽  
Shihao Zhang ◽  
Suyuan Ji ◽  
Luyao Wei ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Antioxidant Defense ◽  
Hippo Pathway ◽  
Ets Transcription Factor ◽  
The Hippo Pathway

scholarly journals Lola regulates Drosophila adult midgut homeostasis via non-canonical hippo signaling

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Xue Hao ◽  
Shimin Wang ◽  
Yi Lu ◽  
Wentao Yu ◽  
Pengyue Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Stem Cell ◽  
Hippo Pathway ◽  
Tissue Homeostasis ◽  
Intestinal Stem Cell ◽  
Hippo Signaling ◽  
Intestinal Function ◽  
Independent Manner ◽  
The Hippo Pathway ◽  
Basal Proliferation

Tissue homeostasis and regeneration in the Drosophila midgut is regulated by a diverse array of signaling pathways including the Hippo pathway. Hippo signaling restricts intestinal stem cell (ISC) proliferation by sequestering the transcription co-factor Yorkie (Yki) in the cytoplasm, a factor required for rapid ISC proliferation under injury-induced regeneration. Nonetheless, the mechanism of Hippo-mediated midgut homeostasis and whether canonical Hippo signaling is involved in ISC basal proliferation are less characterized. Here we identify Lola as a transcription factor acting downstream of Hippo signaling to restrict ISC proliferation in a Yki-independent manner. Not only that Lola interacts with and is stabilized by the Hippo signaling core kinase Warts (Wts), Lola rescues the enhanced ISC proliferation upon Wts depletion via suppressing Dref and SkpA expressions. Our findings reveal that Lola is a non-canonical Hippo signaling component in regulating midgut homeostasis, providing insights on the mechanism of tissue maintenance and intestinal function.

scholarly journals YAP regulates cell size and growth dynamics via non-cell autonomous mediators

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Douaa Mugahid ◽  
Marian Kalocsay ◽  
Xili Liu ◽  
Jonathan Scott Gruver ◽  
Leonid Peshkin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Size ◽  
Cultured Cells ◽  
Hippo Pathway ◽  
Growth Dynamics ◽  
Cell Number ◽  
Hek293 Cells ◽  
Tissue Size ◽  
The Stability ◽  
The Hippo Pathway

The Hippo pathway regulates organ size, regeneration, and cell growth by controlling the stability of the transcription factor, YAP (Yorkie in Drosophila). When there is tissue damage, YAP is activated allowing the restoration of homeostatic tissue size. The exact signals by which YAP is activated are still not fully understood, but its activation is known to affect both cell size and cell number. Here we used cultured cells to examine the coordinated regulation of cell size and number under the control of YAP. Our experiments in isogenic HEK293 cells reveal that YAP can affect cell size and number by independent circuits. Some of these effects are cell autonomous, such as proliferation, while others are mediated by secreted signals. In particular CYR61, a known secreted YAP target, is a non-cell autonomous mediator of cell survival, while another unidentified secreted factor controls cell size.

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