scholarly journals Expression of the Prion Protein Family Member Shadoo Causes Drug Hypersensitivity That Is Diminished by the Coexpression of the Wild Type Prion Protein

2015 ◽  
Vol 291 (9) ◽  
pp. 4473-4486 ◽  
Author(s):  
Antal Nyeste ◽  
Petra Bencsura ◽  
István Vida ◽  
Zoltán Hegyi ◽  
László Homolya ◽  
...  
2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Antal Nyeste ◽  
Claudia Stincardini ◽  
Petra Bencsura ◽  
Milica Cerovic ◽  
Emiliano Biasini ◽  
...  

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4344-4344
Author(s):  
Amanda Scholl ◽  
Kentson Lam ◽  
Alex Muselman ◽  
Tingdong Tang ◽  
Shinobu Matsuura ◽  
...  

Abstract RUNX1 is the transcription factor described as the master regulator of hematopoiesis. Due to its central role during blood development, numerous RUNX1 mutations have been reported in hematologic abnormalities. Mice null for Runx1 die during embryogenesis, lacking definitive HSCs. Conditional Runx1Δ/Δ mice are viable, but exhibit a variety of blood abnormalities. The most salient defect in these Runx1Δ/Δ mice is expansion of the hematopoietic stem and progenitor cell (HSPC) population, measured as an increase in number of lineage negative, Sca1 positive, cKit positive (LSK) cells. A shortened form of RUNX1 (RUNX1SF) lacking the C-terminal and part of the N-terminal domain (41-214) acts as a dominant negative regulator of RUNX1 and hence also models RUNX1 loss-of-function. A differential gene expression analysis of HSPCs derived from Runx1Δ/Δ compared to wild type mice uncovered GTPase immunity-associated protein family member 4 (GIMAP4) as one of the genes most highly upregulated. Previous studies have focused almost exclusively on the role of GIMAP4 as a pro-apoptotic protein during T-cell development. This study illuminates a novel non-apoptotic role of GIMAP4 in a formerly unstudied HSPC context. Runx1Δ/Δ mice were crossed with Gimap4-/- mice to generate a double knockout (dKO) mouse line. These dKO mice exhibited attenuated HSPC proliferation in comparison to Runx1Δ/Δ mice, suggesting that GIMAP4 functions in this HSPC expansion phenotype. BMT experiments using lethally irradiated C57 mice and RUNX1SF transduced wild type versus Gimap4-/-bone marrow confirmed this result. GIMAP4 also worked independently and coordinately with RUNX1 to influence individual progenitor populations. Common lymphoid progenitors (CLP) were affected only by GIMAP4. Gimap4-/- mice exhibited an expansion of the CLP population, consistent with its pro-apoptotic role in lymphoid populations. Conversely, both RUNX1 and GIMAP4 coordinately exerted an effect on myeloid progenitor populations. Runx1Δ/Δ mice harbored expanded granulocyte-macrophage progenitor (GMP) and common myeloid progenitor (CMP) populations. This expansion was not observed when GIMAP4 was also ablated. This suggests a pro-proliferative role of GIMAP4 specifically in myeloid populations. These opposing roles of GIMAP4 in lymphoid versus myeloid cells suggest a more contextual, cell-specific role of this GTPase protein. Ultimately, this study provides insight into how RUNX1 and GIMAP4 may coordinate to maintain HSPC homeostasis. Disclosures No relevant conflicts of interest to declare.


2001 ◽  
Vol 102 (1-2) ◽  
pp. 223-226 ◽  
Author(s):  
Devyn M. Smith ◽  
Lisa A. Collins-Racie ◽  
Valeria A. Marigo ◽  
Drucilla J. Roberts ◽  
Nicole M. Davis ◽  
...  

1998 ◽  
Vol 18 (9) ◽  
pp. 5062-5072 ◽  
Author(s):  
Ronald Boeck ◽  
Bruno Lapeyre ◽  
Christine E. Brown ◽  
Alan B. Sachs

ABSTRACT mRNA in the yeast Saccharomyces cerevisiae is primarily degraded through a pathway that is stimulated by removal of the mRNA cap structure. Here we report that a mutation in the SPB8(YJL124c) gene, initially identified as a suppressor mutation of a poly(A)-binding protein (PAB1) gene deletion, stabilizes the mRNA cap structure. Specifically, we find that thespb8-2 mutation results in the accumulation of capped, poly(A)-deficient mRNAs. The presence of this mutation also allows for the detection of mRNA species trimmed from the 3′ end. These data show that this Sm-like protein family member is involved in the process of mRNA decapping, and they provide an example of 3′-5′ mRNA degradation intermediates in yeast.


2019 ◽  
Vol 7 (10) ◽  
pp. 446 ◽  
Author(s):  
Chanjae Lee ◽  
Nakjun Choi ◽  
Min K. Bae ◽  
Kyungsil Choo ◽  
Sung-Jae Lee

During an oxidative stress-response assay on a putative Dps-like gene-disrupted Δdgeo_0257 mutant strain of radiation-resistant bacterium Deinococcus geothermalis, a non-pigmented colony was observed among the normal reddish color colonies. This non-pigmented mutant cell subsequently displayed higher sensitivity to H2O2. While carotenoid has a role in protecting as scavenger of reactive oxygen species the reddish wild-type strain from radiation and oxidative stresses, it is hypothesized that the carotenoid biosynthesis pathway has been disrupted in the mutant D. geothermalis cell. Here, we show that, in the non-pigmented mutant cell of interest, phytoene desaturase (Dgeo_0524, crtI), a key enzyme in carotenoid biosynthesis, was interrupted by transposition of an ISDge7 family member insertion sequence (IS) element. RNA-Seq analysis between wild-type and Δdgeo_0257 mutant strains revealed that the expression level of ISDge5 family transposases, but not ISDge7 family members, were substantially up-regulated in the Δdgeo_0257 mutant strain. We revealed that the non-pigmented strain resulted from the genomic integration of ISDge7 family member IS elements, which were also highly up-regulated, particularly following oxidative stress. The transposition path for both transposases is a replicative mode. When exposed to oxidative stress in the absence of the putative DNA binding protein Dgeo_0257, a reddish D. geothermalis strain became non-pigmented. This transformation was facilitated by transposition of an ISDge7 family IS element into a gene encoding a key enzyme of carotenoid biosynthesis. Further, we present evidence of additional active transposition by the ISDge5 family IS elements, a gene that was up-regulated during the stationary phase regardless of the presence of oxidative stress.


2006 ◽  
Vol 2 ◽  
pp. S552-S552
Author(s):  
Boe-Hyun Kim ◽  
Jae-Il Kim ◽  
Eun-Kyoung Choi ◽  
Richard I. Carp ◽  
Yong-Sun Kim

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e54982 ◽  
Author(s):  
Nahid N. Jetha ◽  
Valentyna Semenchenko ◽  
David S. Wishart ◽  
Neil R. Cashman ◽  
Andre Marziali

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