scholarly journals Unexpected role for p19INK4d in posttranscriptional regulation of GATA1 and modulation of human terminal erythropoiesis

Blood ◽  
2017 ◽  
Vol 129 (2) ◽  
pp. 226-237 ◽  
Author(s):  
Xu Han ◽  
Jieying Zhang ◽  
Yuanliang Peng ◽  
Minyuan Peng ◽  
Xiao Chen ◽  
...  
Keyword(s):  
Protein Level ◽  
Posttranscriptional Regulation ◽  
Erythroid Differentiation ◽  
Protein Levels ◽  
Key Points ◽  
Terminal Erythroid Differentiation

Key Points Knockdown of CDKI p19INK4d impairs human terminal erythroid differentiation by decreasing GATA1 protein levels. GATA1 protein level is regulated by p19INK4d via the PEBP1-p-ERK-HSP70-GATA1 pathway.

scholarly journals Quantitative analysis of murine terminal erythroid differentiation in vivo: novel method to study normal and disordered erythropoiesis

Blood ◽  
2013 ◽  
Vol 121 (8) ◽  
pp. e43-e49 ◽  
Author(s):  
Jing Liu ◽  
Jianhua Zhang ◽  
Yelena Ginzburg ◽  
Huihui Li ◽  
Fumin Xue ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
Reliable Method ◽  
Erythroid Differentiation ◽  
Key Points ◽  
Novel Method ◽  
Terminal Erythroid Differentiation

Key Points The study establishes a reliable method to quantify differentiating mouse erythroblasts and to monitor terminal mouse erythropoiesis in vivo. Quantitative analysis of erythropoiesis of thalassemia mice revealed stage-specific changes in terminal erythroid differentiation.

scholarly journals Global transcriptome analyses of human and murine terminal erythroid differentiation

Blood ◽  
2014 ◽  
Vol 123 (22) ◽  
pp. 3466-3477 ◽  
Author(s):  
Xiuli An ◽  
Vincent P. Schulz ◽  
Jie Li ◽  
Kunlu Wu ◽  
Jing Liu ◽  
...  
Keyword(s):  
Erythroid Differentiation ◽  
Key Points ◽  
Global Transcriptome ◽  
Transcriptome Analyses ◽  
Significant Stage ◽  
Species Specific ◽  
Terminal Erythroid Differentiation

Key Points Transcriptome analyses of human and murine reveal significant stage and species-specific differences across stages of terminal erythroid differentiation. These transcriptomes provide a significant resource for understanding mechanisms of normal and perturbed erythropoiesis.

p19INK4d Modulates Human Terminal Erythroid Differentiation By Post-Transcriptionally Regulating GATA1 Expression

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 697-697
Author(s):  
Xu Han ◽  
Jieying Zhang ◽  
Yuanliang Peng ◽  
Huiyong Chen ◽  
Xiao Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Late Stage ◽  
Conflicts Of Interest ◽  
Critical Role ◽  
Ectopic Expression ◽  
Erythroid Differentiation ◽  
Hematopoietic Stem ◽  
Erk Activation ◽  
Protein Levels ◽  
Terminal Erythroid Differentiation

Abstract Erythropoiesis is a process during which hematopoietic stem cell (HSCs) are first committed to erythroid progenitors, which subsequently undergo terminal erythroid differentiation to produce mature red blood cells. During terminal erythroid differentiation, proerythroblasts undergo 4-5 mitoses to sequentially generate basophilic erythroblasts, polychromatic erythroblasts and orthochromatic erythroblasts that expel their nuclei to produce enucleated reticulocytes. Terminal erythropoiesis is a tightly regulated process. The most well studied regulatory mechanisms include EPO/EPOR mediated signal transduction and transcription factors among which GATA1 plays critical role. Terminal erythroid differentiation is also tightly coordinated with cell cycle exit, which is regulated by cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors (CDKI), yet their roles in erythropoiesis remain largely undefined. Our RNA-seq of human terminal erythroid differentiation shows that of seven CDKI members, only three of them, p18INK4c, p19INK4d and p27KIP1, are abundantly expressed in erythroid cells and their expressions are significantly upregulated in late stage erythroblasts, which were further confirmed by western blotting analysis. In contrast to demonstrated roles of p18INK4c and p27KIP1 in terminal erythroid differentiation, the function of p19INK4d this process has not been studied. To explore the role of p19INK4d during human erythropoiesis, we employed a shRNA-mediated knockdown approach in CD34+ cells and found that p19INK4d knockdown delayed erythroid differentiation, inhibited cell growth, led to increased apoptosis and generation of abnormally nucleated late stage erythroblasts. Unexpectedly, p19INK4d knockdown did not affect cell cycle. Rather it led to decreased GATA1 protein levels. Importantly, the differentiation and nucleus defects were rescued by ectopic expression of GATA1. As GATA1 protein is protected by nuclear HSP70, to explore the mechanism for the decreased GATA1 protein levels, we examined the effects of p19INK4d knockdown on HSP70 and found p19INK4d knockdown led to decreased nuclear localization of HSP70 due to reduced ERK activation. Further biochemical analysis revealed that p19INK4d directly binds to Ras kinase inhibitor PEBP1 and that p19INK4d knockdown increased the expression of PEBP1 which in turn led to reduced ERK activation. These results demonstrate that p19INK4d maintains GATA1 protein levels through PEBP1-pERK-HSP70-GATA1 pathway. Our findings identify previously unknown and unexpected roles for p19INK4d in human terminal erythroid differentiation via a novel pathway. Disclosures No relevant conflicts of interest to declare.

scholarly journals Modified activin receptor IIB ligand trap mitigates ineffective erythropoiesis and disease complications in murine β-thalassemia

Blood ◽  
2014 ◽  
Vol 123 (25) ◽  
pp. 3864-3872 ◽  
Author(s):  
Rajasekhar N. V. S. Suragani ◽  
Sharon M. Cawley ◽  
Robert Li ◽  
Samantha Wallner ◽  
Mark J. Alexander ◽  
...  
Keyword(s):  
Iron Overload ◽  
Erythroid Differentiation ◽  
Bone Defects ◽  
Ineffective Erythropoiesis ◽  
Activin Receptor ◽  
Key Points ◽  
Terminal Erythroid Differentiation ◽  
Activin Receptor Iib

Key Points Modified ActRIIB ligand trap promotes terminal erythroid differentiation and mitigates ineffective erythropoiesis in murine β-thalassemia. This agent reduces anemia, α-globin aggregates, hemolysis, and disease complications such as iron overload, splenomegaly, and bone defects.

scholarly journals Widespread and dynamic translational control of red blood cell development

Blood ◽  
2017 ◽  
Vol 129 (5) ◽  
pp. 619-629 ◽  
Author(s):  
Juan R. Alvarez-Dominguez ◽  
Xu Zhang ◽  
Wenqian Hu
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Translational Control ◽  
Erythroid Differentiation ◽  
Cell Development ◽  
Key Points ◽  
Terminal Erythroid Differentiation

Key Points Critical roles for dynamic translational control during terminal erythroid differentiation. RBM38 can regulate translation during terminal erythropoiesis.

scholarly journals Severely impaired terminal erythroid differentiation as an independent prognostic marker in myelodysplastic syndromes

2018 ◽  
Vol 2 (12) ◽  
pp. 1393-1402 ◽  
Author(s):  
Abdullah Mahmood Ali ◽  
Yumin Huang ◽  
Ronald Feitosa Pinheiro ◽  
Fumin Xue ◽  
Jingping Hu ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Prognostic Marker ◽  
Myelodysplastic Syndromes ◽  
Erythroid Differentiation ◽  
Independent Prognostic Factor ◽  
Independent Prognostic Marker ◽  
Key Points ◽  
Terminal Erythroid Differentiation

Key Points TED is defective in patients with MDS. TED is an independent prognostic factor for survival in MDS.

scholarly journals Distinct roles for TET family proteins in regulating human erythropoiesis

Blood ◽  
2017 ◽  
Vol 129 (14) ◽  
pp. 2002-2012 ◽  
Author(s):  
Hongxia Yan ◽  
Yaomei Wang ◽  
Xiaoli Qu ◽  
Jie Li ◽  
John Hale ◽  
...  
Keyword(s):  
Erythroid Differentiation ◽  
Erythroid Progenitors ◽  
Key Points ◽  
Terminal Erythroid Differentiation

Key Points TET3 knockdown impairs terminal erythroid differentiation, whereas TET2 knockdown leads to accumulation of erythroid progenitors. Global levels of 5mC are not altered by knockdown of either TET2 or TET3.

The proapoptotic factor Nix is coexpressed with Bcl-xL during terminal erythroid differentiation

Blood ◽  
2003 ◽  
Vol 102 (2) ◽  
pp. 712-717 ◽  
Author(s):  
Wulin Aerbajinai ◽  
Mara Giattina ◽  
Y. Terry Lee ◽  
Mark Raffeld ◽  
Jeffery L. Miller
Keyword(s):  
Culture Medium ◽  
Erythroid Differentiation ◽  
Screening Strategy ◽  
Terminal Phase ◽  
Protein Levels ◽  
Erythroleukemia Cells ◽  
Proteosomal Degradation ◽  
Erythroid Maturation ◽  
Polymerase Chain ◽  
Terminal Erythroid Differentiation

Abstract Transcriptional profiles of cultured primary human erythroid cells were examined to identify those genes involved in the control of erythroid growth during the terminal phase of maturation. Our in silico screening strategy indicated that a hypoxia-inducible proapoptotic member of the Bcl-2 gene family called Nix is expressed during erythropoiesis. We next performed Northern blot analyses and determined that the 1.4-kb Nix transcript is expressed at lower levels in erythroleukemia cells than reticulocytes. Polymerase chain reaction (PCR)–based transcriptional patterning confirmed the increased expression of Nix during human erythropoiesis with a pattern similar to that of Bcl-xL and glycophorin A and opposite that of Bcl-2. Western blot analyses revealed Nix protein levels that were lower than expected due to increased proteosomal degradation. The expression of Nix and Bcl-xL proteins decreased relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) control on the removal of erythropoietin (EPO) from the culture medium. Immunocytochemical analyses demonstrated a similar perinuclear mitochondrial expression pattern for both proteins in hemoglobinized precursors. On the basis of these data, we propose that the proapoptotic factor Nix is a highly regulated effector of growth during terminal erythroid maturation.

scholarly journals The severe phenotype of Diamond-Blackfan anemia is modulated by heat shock protein 70

2017 ◽  
Vol 1 (22) ◽  
pp. 1959-1976 ◽  
Author(s):  
Marc Gastou ◽  
Sarah Rio ◽  
Michaël Dussiot ◽  
Narjesse Karboul ◽  
Hélène Moniz ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein 70 ◽  
Erythroid Differentiation ◽  
Severe Phenotype ◽  
Erythroid Progenitors ◽  
Erythroid Progenitor ◽  
Diamond Blackfan Anemia ◽  
Erythroid Progenitor Cells ◽  
Key Points ◽  
Terminal Erythroid Differentiation

Key Points Proteasomal HSP70 degradation results in cleavage of GATA1, decrease in erythroid progenitors, and apoptosis in severe DBA phenotype. HSP70 plays a role not only during terminal erythroid differentiation, but also in the earlier proliferation of erythroid progenitor cells.

Pengaruh Lama Pengasinan Terhadap Kadar Protein Putih Telur Itik

2014 ◽  
Vol 1 (1) ◽  
pp. 36 ◽  
Author(s):  
Siti Fatimah ◽  
Muji Rahayu ◽  
Siti Aminah
Keyword(s):  
Protein Level ◽  
Egg White ◽  
Special Treatment ◽  
Egg White Protein ◽  
Protein Levels ◽  
Duck Egg ◽  
Egg Period ◽  
Graph Presentation ◽  
And Control ◽  
The Impact

Background : Egg  is one of the animal protein source, which has delicious taste, easy to digest and highly nutritious. Besides its affordable price, its supply availability is unquestionable as well. However, due to its short storability, it requires special treatment, such as preserving, to store it for long period. One way to preserve the egg is by pickling egg, which generally requires seven to ten days of marinating. During the process of marinating, there will be a visual change of egg white and yolk. Their structures  will be more solid (the occurrence of thickening process) because salinization will lead to protein denaturalization. Consequently, it has an influence as well towards the content of egg white protein of duck egg. This study is aimed to explore the impact of various time of pickling egg towards egg white protein of duck egg. Method  : The study where takes place in a laboratories, is a true experimental study for the reason that the researcher must provide intervention, hence all of potentially confounding variables are manageable. Samples that had been used in this study are duck eggs which were bought from North Brebes. This study is expected to generate data from four various time of pickling egg and control (no treatment). Since there are four samples, accordingly the number of data resulted are twenty. The resulted data will be descriptively presented in table, graph, presentation, and narration. Result  : Protein level examination within duck white egg shows changes  in protein levels that occurs in every variation of pickling egg time, where the average results of the assay of duck egg white protein is 14.94% without treatment (control), in five days of pickling time is 13.68%, in seven days of pickling time is 13.29%, in nine days of pickling time is 12.87% and eleven days of pickling time is 12.78%. Conclusion  : There is a significant impact among the period of pickling time to the protein level degradation of duck white egg. Keywords : Duck egg, period of pickling time, level protein of duck white egg.

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