scholarly journals Enhancer of Polycomb and the Tip60 complex repress hematological tumor initiation by negatively regulating JAK/STAT pathway activity

2019 ◽  
Vol 12 (5) ◽  
pp. dmm038679 ◽  
Author(s):  
Alessandro A. Bailetti ◽  
Lenny J. Negrón-Piñeiro ◽  
Vishal Dhruva ◽  
Sneh Harsh ◽  
Sean Lu ◽  
...  
Keyword(s):  
Tumor Initiation ◽  
Pathway Activity ◽  
Hematological Tumor ◽  
Stat Pathway

scholarly journals DMM Outstanding Paper Prize 2019 winner: Alessandro Bailetti

2020 ◽  
Vol 13 (8) ◽  
pp. dmm046672
Author(s):  
Rachel Hackett
Keyword(s):  
Outstanding Contribution ◽  
Disease Models ◽  
Tumor Initiation ◽  
Pathway Activity ◽  
Hematological Tumor ◽  
Stat Pathway

ABSTRACTDisease Models & Mechanisms (DMM) is delighted to announce (with apologies for the delay) that the winner of the DMM Prize 2019 is Alessandro Bailetti, for his paper entitled ‘Enhancer of Polycomb and the Tip60 complex repress hematological tumor initiation by negatively regulating JAK/STAT pathway activity’ ( Bailetti et al., 2019). The prize of $1000 is awarded to the first author of the paper that is judged by the journal's editors to be the most outstanding contribution to the journal that year. To be considered for the prize, the first author must be a student or a postdoc of no more than 5 years standing.

scholarly journals Retinal ganglion cell survival after severe optic nerve injury is modulated by crosstalk between JAK/STAT signaling and innate immune responses in the zebrafish retina

Development ◽  
2021 ◽  
Author(s):  
Si Chen ◽  
Kira L. Lathrop ◽  
Takaaki Kuwajima ◽  
Jeffrey M. Gross
Keyword(s):  
Optic Nerve ◽  
Immune Responses ◽  
Ganglion Cell ◽  
Nerve Injury ◽  
Retinal Ganglion Cell ◽  
Visual Information ◽  
Retinal Ganglion ◽  
Optic Nerve Injury ◽  
Pathway Activity ◽  
Stat Pathway

Visual information is transmitted from the eye to the brain along the optic nerve, a structure composed of retinal ganglion cell (RGC) axons. The optic nerve is highly vulnerable to damage in neurodegenerative diseases like glaucoma and there are currently no FDA-approved drugs or therapies to protect RGCs from death. Zebrafish possess remarkable neuroprotective and regenerative abilities and here, utilizing an optic nerve transection (ONT) injury and an RNA-seq-based approach, we identify genes and pathways active in RGCs that may modulate their survival. Through pharmacological perturbation, we demonstrate that JAK/STAT pathway activity is required for RGC survival after ONT. Furthermore, we show that immune responses directly contribute to RGC death after ONT; macrophages/microglia are recruited to the retina and blocking neuroinflammation or depleting these cells after ONT rescues survival of RGCs. Taken together, these data support a model in which crosstalk between macrophages/microglia and RGCs, mediated by Jak/Stat pathway activity, regulates RGC survival after optic nerve injury.

scholarly journals Opposing Wnt and JAK-STAT signaling gradients define a stem cell domain by regulating spatially patterned cell division and differentiation at two borders

2020 ◽  
Author(s):  
David Melamed ◽  
Daniel Kalderon
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Adult Stem Cells ◽  
Wnt Pathway ◽  
Opposite Polarity ◽  
Follicle Cells ◽  
Pathway Activity ◽  
Stat Signaling ◽  
Stat Pathway

AbstractMany adult stem cells are maintained as a community by population asymmetry, wherein stochastic actions of individual cells collectively result in a balance between stem cell division and differentiation. We have used Drosophila Follicle Stem Cells (FSCs) as a paradigm to explore the extracellular niche signals that define a stem cell domain and organize stem cell behavior. FSCs produce transit-amplifying Follicle Cells (FCs) from their posterior face and quiescent Escort Cells (ECs) to their anterior. Here we show that JAK-STAT pathway activity, which declines from posterior to anterior, dictates the pattern of divisions over the FSC and EC domains, promotes more posterior FSC locations and conversion to FCs, while opposing EC production. A Wnt pathway gradient of opposite polarity promotes more anterior FSC locations and EC production and opposes FC production. Promotion of both FSC division and conversion to FCs by JAK-STAT signaling buffers the effects of genetically altered pathway activity on FSC numbers and balances the four-fold higher rate of differentiation at the posterior face of the FSC domain with a higher rate of FSC division in the most posterior layer. However, genetic elimination of Wnt pathway activity exacerbated elevated FC production resulting from increased JAK-STAT pathway activity, leading to rapid FSC depletion despite high rates of division. The two pathways combine to define a stem cell domain through concerted effects on FSC differentiation to ECs (high Wnt, low JAK-STAT) and FCs (low Wnt, high JAK-STAT) at each end of opposing signaling gradients, further enforced by quiescence at the anterior border due to declining JAK-STAT pathway activity.

scholarly journals Opposing JAK-STAT and Wnt signaling gradients define a stem cell domain by regulating differentiation at two borders

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
David Melamed ◽  
Daniel Kalderon
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Wnt Pathway ◽  
Adult Stem Cell ◽  
Follicle Cells ◽  
Pathway Activity ◽  
Stem Cell Division ◽  
Follicle Stem Cells ◽  
Stat Pathway

Many adult stem cell communities are maintained by population asymmetry, where stochastic behaviors of multiple individual cells collectively result in a balance between stem cell division and differentiation. We investigated how this is achieved for Drosophila Follicle Stem Cells (FSCs) by spatially-restricted niche signals. FSCs produce transit-amplifying Follicle Cells (FCs) from their posterior face and quiescent Escort Cells (ECs) to their anterior. We show that JAK-STAT pathway activity, which declines from posterior to anterior, dictates the pattern of divisions over the FSC domain, promotes more posterior FSC locations and conversion to FCs, while opposing EC production. Wnt pathway activity declines from the anterior, promotes anterior FSC locations and EC production, and opposes FC production. The pathways combine to define a stem cell domain through concerted effects on FSC differentiation to ECs and FCs at either end of opposing signaling gradients, and impose a pattern of proliferation that matches derivative production.

scholarly journals Drosophila SOCS36E negatively regulates JAK/STAT pathway signaling via two separable mechanisms

2013 ◽  
Vol 24 (18) ◽  
pp. 3000-3009 ◽  
Author(s):  
Wojciech Stec ◽  
Oscar Vidal ◽  
Martin P. Zeidler
Keyword(s):  
Janus Kinase ◽  
Physical Interaction ◽  
Pathway Activity ◽  
Lower Organism ◽  
Independent Mechanism ◽  
Cullin 5 ◽  
Socs Proteins ◽  
Ligand Stimulation ◽  
Socs Box ◽  
Stat Pathway

Conserved from humans to Drosophila, the Janus kinase/signal transducer and activators of transcription (JAK/STAT) signaling cascade is essential for multiple developmental and homeostatic processes, with regulatory molecules controlling pathway activity also highly conserved. We characterize the Drosophila JAK/STAT pathway regulator SOCS36E and show that it functions via two independent mechanisms. First, we show that Drosophila Elongin B/C and Cullin-5 act via the SOCS-box of SOCS36E to reduce pathway activity specifically in response to ligand stimulation—a process that involves endocytic trafficking and lysosomal degradation of the Domeless (Dome) receptor. Second, SOCS36E also suppresses both stimulated and basal pathway activity via an Elongin/Cullin-independent mechanism that is mediated by the N-terminus of SOCS36E, which is required for the physical interaction of SOCS36E with Dome. Although some human SOCS proteins contain N-terminal kinase-inhibitory domains, we do not identify such a region in SOCS36E and propose a model wherein the N-terminal of SOCS36E blocks access to tyrosine residues in Dome. Our biochemical analysis of a SOCS-family regulator from a lower organism highlights the fundamental conserved roles played by regulatory mechanisms in signal transduction.

442: Stromal Hedgehog Pathway Activity Accelerates Prostate Tumor Growth

2006 ◽  
Vol 175 (4S) ◽  
pp. 143-143
Author(s):  
Aubie Shaw ◽  
Jerry Gipp ◽  
Wade Bushman
Keyword(s):  
Tumor Growth ◽  
Prostate Tumor ◽  
Hedgehog Pathway ◽  
Pathway Activity

Role of JAK-STAT pathway in pulmonary fibrosis

Pneumologie ◽  
2013 ◽  
Vol 67 (05) ◽  
Author(s):  
J Eschenbrenner ◽  
W Janssen ◽  
B Kojonazarov ◽  
K Murmann ◽  
A Ghofrani ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Stat Pathway

YAP-induced tumor initiation mediates a switch in hepatic macrophage identity via the Ccl2/Ccr2 axis

2020 ◽  
Author(s):  
S Thomann ◽  
S Weiler ◽  
T Wei ◽  
C Sticht ◽  
C De La Torre ◽  
...  
Keyword(s):  
Tumor Initiation ◽  
Hepatic Macrophage
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