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Title: Acidic leucine-rich nuclear phosphoprotein 32 family member B (ANP32B) contributes to retinoic acid-induced differentiation of leukemic cells

Abstract

Highlights: Black-Right-Pointing-Pointer ANP32B was down-regulated during ATRA-induced leukemic cell differentiation. Black-Right-Pointing-Pointer Knockdown of ANP32B enhanced ATRA-induced leukemic cell differentiation. Black-Right-Pointing-Pointer Ectopic expression of ANP32B inhibited ATRA-induced leukemic cell differentiation. Black-Right-Pointing-Pointer ANP32B inhibited ATRA activated transcriptional activity of RAR{alpha}. -- Abstract: The acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) is a member of a conserved superfamily of nuclear proteins whose functions are largely unknown. In our previous work, ANP32B was identified as a novel direct substrate for caspase-3 and acted as a negative regulator for leukemic cell apoptosis. In this work, we provided the first demonstration that ANP32B expression was down-regulated during differentiation induction of leukemic cells by all-trans retinoic acid (ATRA). Knockdown of ANP32B expression by specific shRNA enhanced ATRA-induced leukemic cell differentiation, while ectopic expression of ANP32B attenuated it, indicating an inhibitory role of ANP32B against leukemic cell differentiation. Furthermore, luciferase reporter assay revealed that ANP32B might exert this role through inhibiting the ATRA dependent transcriptional activity of retinoic acid receptor (RAR{alpha}). These data will shed new insights into understanding the biological functions of ANP32B protein.

Authors:
; ; ; ;  [1];  [1]
  1. Shanghai Universities E-Institute for Chemical Biology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China)
Publication Date:
OSTI Identifier:
22207940
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 423; Journal Issue: 4; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BIOLOGICAL FUNCTIONS; CELL DIFFERENTIATION; LEUCINE; LUCIFERASE; PHOSPHOPROTEINS; RECEPTORS; RETINOIC ACID

Citation Formats

Yu, Yun, Shen, Shao-Ming, Zhang, Fei-Fei, Wu, Zhao-Xia, Han, Bin, and Wang, Li-Shun, E-mail: jywangls@shsmu.edu.cn. Acidic leucine-rich nuclear phosphoprotein 32 family member B (ANP32B) contributes to retinoic acid-induced differentiation of leukemic cells. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2012.06.025.
Yu, Yun, Shen, Shao-Ming, Zhang, Fei-Fei, Wu, Zhao-Xia, Han, Bin, & Wang, Li-Shun, E-mail: jywangls@shsmu.edu.cn. Acidic leucine-rich nuclear phosphoprotein 32 family member B (ANP32B) contributes to retinoic acid-induced differentiation of leukemic cells. United States. doi:10.1016/J.BBRC.2012.06.025.
Yu, Yun, Shen, Shao-Ming, Zhang, Fei-Fei, Wu, Zhao-Xia, Han, Bin, and Wang, Li-Shun, E-mail: jywangls@shsmu.edu.cn. 2012. "Acidic leucine-rich nuclear phosphoprotein 32 family member B (ANP32B) contributes to retinoic acid-induced differentiation of leukemic cells". United States. doi:10.1016/J.BBRC.2012.06.025.
@article{osti_22207940,
title = {Acidic leucine-rich nuclear phosphoprotein 32 family member B (ANP32B) contributes to retinoic acid-induced differentiation of leukemic cells},
author = {Yu, Yun and Shen, Shao-Ming and Zhang, Fei-Fei and Wu, Zhao-Xia and Han, Bin and Wang, Li-Shun, E-mail: jywangls@shsmu.edu.cn},
abstractNote = {Highlights: Black-Right-Pointing-Pointer ANP32B was down-regulated during ATRA-induced leukemic cell differentiation. Black-Right-Pointing-Pointer Knockdown of ANP32B enhanced ATRA-induced leukemic cell differentiation. Black-Right-Pointing-Pointer Ectopic expression of ANP32B inhibited ATRA-induced leukemic cell differentiation. Black-Right-Pointing-Pointer ANP32B inhibited ATRA activated transcriptional activity of RAR{alpha}. -- Abstract: The acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) is a member of a conserved superfamily of nuclear proteins whose functions are largely unknown. In our previous work, ANP32B was identified as a novel direct substrate for caspase-3 and acted as a negative regulator for leukemic cell apoptosis. In this work, we provided the first demonstration that ANP32B expression was down-regulated during differentiation induction of leukemic cells by all-trans retinoic acid (ATRA). Knockdown of ANP32B expression by specific shRNA enhanced ATRA-induced leukemic cell differentiation, while ectopic expression of ANP32B attenuated it, indicating an inhibitory role of ANP32B against leukemic cell differentiation. Furthermore, luciferase reporter assay revealed that ANP32B might exert this role through inhibiting the ATRA dependent transcriptional activity of retinoic acid receptor (RAR{alpha}). These data will shed new insights into understanding the biological functions of ANP32B protein.},
doi = {10.1016/J.BBRC.2012.06.025},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 423,
place = {United States},
year = 2012,
month = 7
}
  • All-trans retinoic acid (ATRA) induces complete remission in a high proportion of patients with acute promyelocytic leukemia (APL); however, the response is sometimes very slow. Furthermore, relapse and resistance to treatment often occur despite continued treatment with ATRA. Thereafter, combination treatment strategies have been suggested to circumvent these problems. The present study demonstrates that caffeic acid phenethyl ester (CAPE), a major component of honeybee propolis, enhanced ATRA-induced granulocytic differentiation in HL-60, a human promyelocytic cell line. The differentiation was assessed by Wright-Giemsa stain, nitroblue tetrazolium reduction, and membrane differentiation marker CD11b. In addition, CAPE enhanced ATRA-induced cell cycle arrest atmore » the G1 phase by decreasing the association of cdk2-cyclin E complex. Finally, it was demonstrated that CAPE promoted the ATRA-mediated nuclear transcription activation of RAR{alpha} assessed by EMSA assay and enhanced the expression of target genes including RAR{alpha}, C/EBP{epsilon}, and p21 protein resulting in the differentiation development of leukemia. It is suggested that CAPE possesses the potential to enhance the efficiency of ATRA in the differentiation therapy of APL.« less
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  • Highlights: Black-Right-Pointing-Pointer TRIM32 enhanced RAR{alpha}-mediated transcriptional activity even in the absence of RA. Black-Right-Pointing-Pointer TRIM32 stabilized RAR{alpha} in the human promyelogenous leukemic cell line HL60. Black-Right-Pointing-Pointer Overexpression of TRIM32 in HL60 cells induced granulocytic differentiation. Black-Right-Pointing-Pointer TRIM32 may function as a coactivator for RAR{alpha}-mediated transcription in APL cells. -- Abstract: Ubiquitination, one of the posttranslational modifications, appears to be involved in the transcriptional activity of nuclear receptors including retinoic acid receptor {alpha} (RAR{alpha}). We previously reported that an E3 ubiquitin ligase, TRIM32, interacts with several important proteins including RAR{alpha} and enhances transcriptional activity of RAR{alpha} in mouse neuroblastoma cells andmore » embryonal carcinoma cells. Retinoic acid (RA), which acts as a ligand to nuclear receptors including RAR{alpha}, plays crucial roles in development, differentiation, cell cycles and apoptosis. In this study, we found that TRIM32 enhances RAR{alpha}-mediated transcriptional activity even in the absence of RA and stabilizes RAR{alpha} in the human promyelogenous leukemic cell line HL60. Moreover, we found that overexpression of TRIM32 in HL60 cells suppresses cellular proliferation and induces granulocytic differentiation even in the absence of RA. These findings suggest that TRIM32 functions as one of the coactivators for RAR{alpha}-mediated transcription in acute promyelogenous leukemia (APL) cells, and thus TRIM32 may become a potentially therapeutic target for APL.« less