The transcription factor ATF5: role in cellular differentiation, stress responses, and cancer

Sears, Thomas K.; Angelastro, James M.

doi:10.18632/oncotarget.21102

Cited by 34 publications

(32 citation statements)

References 78 publications

(123 reference statements)

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“…Furthermore, MSCs are susceptible to apoptosis induced by ER stress, and blockage of ER stress promoted the survival of MSCs under H/SD conditions (27). In response to ER stress, there is an upregulation of ER chaperones such as CHOP and ATF4 (28). In the present study, CHOP and ATF4 expression levels were upregulated under H/SD conditions and treatment with UTI could reverse this effect.…”

Section: Discussionsupporting

confidence: 50%

Ulinastatin inhibits apoptosis induced by serum deprivation in mesenchymal stem cells

Shi

et al. 2019

Mol Med Report

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Mesenchymal stem cells (MSCs) have exhibited great potential in the therapy of cardiovascular disease. However, the application of MSCs is hampered by apoptosis, which reduces the number of cells in the host cardiac microenvironment. Ulinastatin (UTI), a broad-spectrum protease inhibitor that can be purified from human urine, has attracted attention for its protective effects through its immunomodulatory and anti-inflammatory properties. The present study aimed to evaluate the effects of UTI on serum deprivation-induced apoptosis of MSCs and investigate its molecular mechanisms. Cell viability was determined by the MTT assay. Apoptosis was assessed by flow cytometric analysis with Annexin V/propidium iodide staining. The protein levels of cleaved caspase-3, B-cell lymphoma-2 (Bcl-2) family proteins, total-Akt and phospho-Akt were evaluated by western blot. The results of the present study demonstrated that UTI exhibited a protective effect in serum deprived MSCs, as indicated by increased cell viability, and a reduction in the rate of apoptosis and caspase-3 activation. In addition, treatment with UTI significantly decreased the expression levels of Bcl-2, Bcl-extra large and Bcl-associated X protein. Furthermore, activation of the Akt signaling pathway was involved in the UTI-induced anti-apoptotic effects. The present findings indicated that UTI is able to promote the survival of MSCs under serum deprivation conditions. The present study may be helpful in improving the therapeutic efficacy of MSC transplantation used to cure chronic ischemic heart disease.

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Section: Discussionsupporting

confidence: 50%

Ulinastatin inhibits apoptosis induced by serum deprivation in mesenchymal stem cells

Shi

et al. 2019

Mol Med Report

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“…ATF5 is involved in the integrated stress responses (ISR) through regulating endoplasmic reticulum unfolded protein response (UPR) and cytosolic heat shock response (Sears & Angelastro, 2017), similar to the role of ATF4, which is regulated by HRI in iron-deficient erythropoiesis (Chen, 2014). HRI-mediated ISR is necessary for effective erythropoiesis in iron deficiency (Zhang et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

“…As a member of the ATF/cAMP response‐element binding protein (CREB) family, activating transcription factor 5 (ATF5) serves as an anti‐apoptotic transcription factor and regulates cell proliferation and differentiation during the development of many tissues (Sears & Angelastro, ). Dysregulated ATF5 has been reported to be involved in the progression of diabetes and a variety of cancers, such as leukaemia, lymphoma, glioma, lung and breast cancers (Sears & Angelastro, ). However, the diverse roles of ATF5 are tissue‐specific, as demonstrated by the promotion of hepatic differentiation (Du et al , ) and olfactory bulb development (Wang et al , ) but inhibition of osteogenesis (Leong et al , ) and other types of neurogenesis (Angelastro et al , ).…”

mentioning

confidence: 99%

Requirement of activating transcription factor 5 for murine fetal liver erythropoiesis

Zhang

Chen

2019

Br J Haematol

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Activating transcription factor 5 (ATF5) is necessary for the development of various tissues, particularly under stress. Dysfunctions of ATF5 have been shown to be involved in many diseases. The exact function of ATF5 is tissue‐specific, and its role in erythropoiesis is still unknown. We here employed the loss of function strategy to investigate the role of ATF5 in murine erythropoiesis. We found that knockdown of Atf5 impaired the proliferation of fetal liver erythroid progenitors. Furthermore, erythroid differentiation was inhibited by ATF5 deficiency. Our study suggests that ATF5 may be a potential therapeutic target for treating blood diseases with ineffective erythropoiesis.

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“…In addition, a large number of genes are increased by the Try‐19 phosphorylation of SRSF1 (): chemokine (C‐X‐C) ligand 1 ( CXCL1 ), activating transcription factor 5 ( ATF5 ), and ATP/GTP binding protein‐like 2 ( AGBL2 ). Studies showed elevated CXCL1 is associated with tumor progression and poor prognosis in cancers; and the overexpression of ATF5 or AGBL2 enhances malignancy in cancer cells . The mechanisms of SRSF1 within different cellular compartments need to be further studied.…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation of serine/arginine‐rich splicing factor 1 at tyrosine 19 promotes cell proliferation in pediatric acute lymphoblastic leukemia

Zhang

Mei

et al. 2018

Cancer Science

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Serine/arginine‐rich splicing factor 1 (SRSF1) has been linked to various human cancers including pediatric acute lymphoblastic leukemia (ALL). Our previous study has shown that SRSF1 potentially contributes to leukemogenesis; however, its underlying mechanism remains unclear. In this study, leukemic cells were isolated from pediatric ALL bone marrow samples, followed by immunoprecipitation assays and mass spectrometry analysis specific to SRSF1. Subcellular localization of the SRSF1 protein and its mutants were analyzed by immunofluorescence staining. Cell growth, colony formation, cell apoptosis, and the cell cycle were investigated using stable leukemic cell lines generated with lentivirus‐mediated overexpressed WT or mutant plasmids. Cytotoxicity of the Tie2 kinase inhibitor was also evaluated. Our results showed the phosphorylation of SRSF1 at tyrosine 19 (Tyr‐19) was identified in newly diagnosed ALL samples, but not in complete remission or normal control samples. Compared to the SRSF1 WT cells, the missense mutants of the Tyr‐19 phosphorylation affected the subcellular localization of SRSF1. In addition, the Tyr‐19 phosphorylation of SRSF1 also led to increased cell proliferation and enhanced colony‐forming properties by promoting the cell cycle. Remarkably, we further identified the kinase Tie2 as a potential therapeutic target in leukemia cells. In conclusion, we identify for the first time that the phosphorylation state of SRSF1 is linked to different phases in pediatric ALL. The Tyr‐19 phosphorylation of SRSF1 disrupts its subcellular localization and promotes proliferation in leukemia cells by driving cell‐cycle progression. Inhibitors targeting Tie2 kinase that could catalyze Tyr‐19 phosphorylation of SRSF1 offer a promising therapeutic target for treatment of pediatric ALL.

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The transcription factor ATF5: role in cellular differentiation, stress responses, and cancer

Cited by 34 publications

References 78 publications

Ulinastatin inhibits apoptosis induced by serum deprivation in mesenchymal stem cells

Ulinastatin inhibits apoptosis induced by serum deprivation in mesenchymal stem cells

Requirement of activating transcription factor 5 for murine fetal liver erythropoiesis

Phosphorylation of serine/arginine‐rich splicing factor 1 at tyrosine 19 promotes cell proliferation in pediatric acute lymphoblastic leukemia

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