PML-RARα induces all-trans retinoic acid-dependent transcriptional activation through interaction with MED1

被引:0
|
作者
Fukuoka, Tomoya [1 ]
Kawai, Asami [1 ]
Takahara, Taku [1 ]
Mori, Mahiro [1 ]
Roeder, Robert G. [2 ]
Hasegawa, Natsumi [1 ]
Ito, Mitsuhiro [1 ,2 ]
机构
[1] Kobe Univ, Div Med Biophys, Lab Hematol, Grad Sch Hlth Sci, Kobe, Hyogo, Japan
[2] Rockefeller Univ, Lab Biochem & Mol Biol, 1230 York Ave, New York, NY 10021 USA
来源
TRANSCRIPTION-AUSTIN | 2019年 / 10卷 / 03期
基金
日本学术振兴会;
关键词
PML-RAR alpha; transcriptional activation; Mediator; MED1; LxxLL nuclear receptor recognition motifs; ACUTE PROMYELOCYTIC LEUKEMIA; COACTIVATOR COMPLEX; THYROID-HORMONE; HISTONE DEACETYLASE; MEDIATOR COMPLEX; TRANSLOCATION; RECRUITMENT; PROTEINS; T(15-17); TRAP220;
D O I
10.1080/21541264.2019.1624467
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Transcriptional activation by PML-RAR alpha, an acute promyelocytic leukemia-related oncofusion protein, requires pharmacological concentrations of all-trans retinoic acid (ATRA). However, the mechanism by which the liganded PML-RAR alpha complex leads to the formation of the preinitiation complex has been unidentified. Here we demonstrate that the Mediator subunit MED1 plays an important role in the ATRA-dependent activation of the PML-RAR alpha-bound promoter. Luciferase reporter assays showed that PML-RAR alpha induced significant transcription at pharmacological doses (1 mu M) of ATRA; however, this was submaximal and equivalent to the level of transcription driven by intact RAR alpha at physiological doses (1 nM) of ATRA. Transcription depended upon the interaction of PML-RAR alpha with the two LxxLL nuclear receptor recognition motifs of MED1, and LxxLL -> LxxAA mutations led to minimal transcription. Mechanistically, MED1 interacted ATRA-dependently with the RAR alpha portion of PML-RAR alpha through the two LxxLL motifs of MED1. These results suggest that PML-RAR alpha initiates ATRA-induced transcription through its interaction with MED1.
引用
收藏
页码:147 / 156
页数:10
相关论文
共 50 条
  • [1] PML-RARα-positive cells contribute to scrotal ulceration with all-trans retinoic acid
    Imataki, Osamu
    Yoshida, Shunsuke
    Kaji, Tomohiro
    Kida, Jun-ichiro
    Kubo, Hiroyuki
    Uemura, Makiko
    Fujita, Haruyuki
    Kadowaki, Norimitsu
    INTERNATIONAL JOURNAL OF DERMATOLOGY, 2022, 61 (03) : E98 - E99
  • [2] A case of acute eosinophilic granulocytic leukemia with PML-RAR alpha fusion gene expression and response to all-trans retinoic acid
    R-Q Yu
    W Huang
    S-J Chen
    S-D Jiang
    Z Chen
    Leukemia, 1997, 11 : 609 - 611
  • [3] The cleavage product ΔPML-RARα contributes to all-trans retinoic acid-mediated differentiation in acute promyelocytic leukemia cells
    Jing, Y
    Xia, LJ
    Lu, M
    Waxman, S
    ONCOGENE, 2003, 22 (26) : 4083 - 4091
  • [4] Relapse of acute promyelocytic leukemia with PML-RARα mutant subclones independent of proximate all-trans retinoic acid selection pressure
    Gallagher, RE
    Schachter-Tokarz, EL
    Zhou, DC
    Ding, W
    Kim, SH
    Sankoorikal, BJ
    Bi, W
    Livak, KJ
    Slack, JL
    Willman, CL
    LEUKEMIA, 2006, 20 (04) : 556 - 562
  • [5] A case of acute eosinophilic granulocytic leukemia with PML-RAR alpha fusion gene expression and response to all-trans retinoic acid
    Yu, RQ
    Huang, W
    Chen, SJ
    Jiang, SD
    Chen, Z
    LEUKEMIA, 1997, 11 (04) : 609 - 611
  • [6] Relapse of acute promyelocytic leukemia with PML-RARα mutant subclones independent of proximate all-trans retinoic acid selection pressure
    R E Gallagher
    E L Schachter-Tokarz
    D-C Zhou
    W Ding
    S H Kim
    B J Sankoorikal
    W Bi
    K J Livak
    J L Slack
    C L Willman
    Leukemia, 2006, 20 : 556 - 562
  • [7] Identification of a novel cDNA regulated by all-trans retinoic acid (ATRA) in a myeloid cell line expressing PML-RAR alpha.
    Yu, M
    Slack, JL
    BLOOD, 1997, 90 (10) : 1436 - 1436
  • [8] All-trans retinoic acid (RA)-dependent potentiation of therapy-related mutant PML-RARα fusion genes by histone deacetylase (HDAC) inhibitors in vitro.
    Zhou, DC
    Kim, SH
    Warrell, RP
    Gallagher, RE
    BLOOD, 2000, 96 (11) : 309A - 309A
  • [9] Arsenic trioxide cooperates with all-trans retinoic acid to enhance mitogen-activated protein kinase activation and differentiation in PML-RARα negative human myeloblastic leukemia cells
    Nayak, Satyaprakash
    Shen, Miaoqing
    Bunaciu, Rodica P.
    Bloom, Stephen E.
    Varner, Jeffrey D.
    Yen, Andrew
    LEUKEMIA & LYMPHOMA, 2010, 51 (09) : 1734 - 1747
  • [10] Leukemic cellular retinoic acid resistance and missense mutations in the PML-RARα fusion gene after relapse of acute promyelocytic leukemia from treatment with all-trans retinoic acid and intensive chemotherapy
    Ding, W
    Li, YP
    Nobile, LM
    Grills, G
    Carrera, I
    Paietta, E
    Tallman, MS
    Wiernik, PH
    Gallagher, RE
    BLOOD, 1998, 92 (04) : 1172 - 1183