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Regulation of Trib2 by an E2F1-C/EBPalpha feedback loop in AML cell proliferation

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Harvard

Rishi, L, Hannon, M, Salomè, M, Hasemann, M, Frank, AK, Campos, J, Timoney, J, O'Connor, C, Cahill, MR, Porse, B & Keeshan, K 2014, 'Regulation of Trib2 by an E2F1-C/EBPalpha feedback loop in AML cell proliferation', Blood, vol. 123, no. 15, pp. 2389-400. https://doi.org/10.1182/blood-2013-07-511683

APA

Rishi, L., Hannon, M., Salomè, M., Hasemann, M., Frank, A. K., Campos, J., Timoney, J., O'Connor, C., Cahill, M. R., Porse, B., & Keeshan, K. (2014). Regulation of Trib2 by an E2F1-C/EBPalpha feedback loop in AML cell proliferation. Blood, 123(15), 2389-400. https://doi.org/10.1182/blood-2013-07-511683

CBE

Rishi L, Hannon M, Salomè M, Hasemann M, Frank AK, Campos J, Timoney J, O'Connor C, Cahill MR, Porse B, Keeshan K. 2014. Regulation of Trib2 by an E2F1-C/EBPalpha feedback loop in AML cell proliferation. Blood. 123(15):2389-400. https://doi.org/10.1182/blood-2013-07-511683

MLA

Vancouver

Author

Rishi, Loveena ; Hannon, Maura ; Salomè, Mara ; Hasemann, Marie ; Frank, Anne Katrine ; Campos, Joana ; Timoney, Jennifer ; O'Connor, Caitriona ; Cahill, Mary R ; Porse, Bo ; Keeshan, Karen. / Regulation of Trib2 by an E2F1-C/EBPalpha feedback loop in AML cell proliferation. In: Blood. 2014 ; Vol. 123, No. 15. pp. 2389-400.

Bibtex

@article{8ecf19840f584df69bd30e66206c1671,
title = "Regulation of Trib2 by an E2F1-C/EBPalpha feedback loop in AML cell proliferation",
abstract = "The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene Trib2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by C/EBPalpha-p42, occurs in acute myeloid leukemia (AML) resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop for E2F1, C/EBPalpha and Trib2 in AML cell proliferation and survival. Further analyses revealed that E2F1-mediated Trib2 expression was repressed by C/EBPalpha-p42, and in normal GMP cells we detect C/EBPalpha bound to the Trib2 promoter. Pharmacological inhibition of the cell cycle or Trib2 knockdown resulted in a block in AML cell proliferation. Our work proposes a novel paradigm whereby E2F1 plays a key role in the regulation of Trib2 expression important for AML cell proliferation control. Importantly, we identify the contribution of dysregulated C/EBPalpha and E2F1 to elevated Trib2 expression and leukemic cell survival, which likely contributes to the initiation and maintenance of AML and may have significant implications for normal and malignant haematopoiesis.",
author = "Loveena Rishi and Maura Hannon and Mara Salom{\`e} and Marie Hasemann and Frank, {Anne Katrine} and Joana Campos and Jennifer Timoney and Caitriona O'Connor and Cahill, {Mary R} and Bo Porse and Karen Keeshan",
year = "2014",
month = feb,
day = "10",
doi = "10.1182/blood-2013-07-511683",
language = "English",
volume = "123",
pages = "2389--400",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "15",

}

RIS

TY - JOUR

T1 - Regulation of Trib2 by an E2F1-C/EBPalpha feedback loop in AML cell proliferation

AU - Rishi, Loveena

AU - Hannon, Maura

AU - Salomè, Mara

AU - Hasemann, Marie

AU - Frank, Anne Katrine

AU - Campos, Joana

AU - Timoney, Jennifer

AU - O'Connor, Caitriona

AU - Cahill, Mary R

AU - Porse, Bo

AU - Keeshan, Karen

PY - 2014/2/10

Y1 - 2014/2/10

N2 - The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene Trib2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by C/EBPalpha-p42, occurs in acute myeloid leukemia (AML) resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop for E2F1, C/EBPalpha and Trib2 in AML cell proliferation and survival. Further analyses revealed that E2F1-mediated Trib2 expression was repressed by C/EBPalpha-p42, and in normal GMP cells we detect C/EBPalpha bound to the Trib2 promoter. Pharmacological inhibition of the cell cycle or Trib2 knockdown resulted in a block in AML cell proliferation. Our work proposes a novel paradigm whereby E2F1 plays a key role in the regulation of Trib2 expression important for AML cell proliferation control. Importantly, we identify the contribution of dysregulated C/EBPalpha and E2F1 to elevated Trib2 expression and leukemic cell survival, which likely contributes to the initiation and maintenance of AML and may have significant implications for normal and malignant haematopoiesis.

AB - The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene Trib2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by C/EBPalpha-p42, occurs in acute myeloid leukemia (AML) resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop for E2F1, C/EBPalpha and Trib2 in AML cell proliferation and survival. Further analyses revealed that E2F1-mediated Trib2 expression was repressed by C/EBPalpha-p42, and in normal GMP cells we detect C/EBPalpha bound to the Trib2 promoter. Pharmacological inhibition of the cell cycle or Trib2 knockdown resulted in a block in AML cell proliferation. Our work proposes a novel paradigm whereby E2F1 plays a key role in the regulation of Trib2 expression important for AML cell proliferation control. Importantly, we identify the contribution of dysregulated C/EBPalpha and E2F1 to elevated Trib2 expression and leukemic cell survival, which likely contributes to the initiation and maintenance of AML and may have significant implications for normal and malignant haematopoiesis.

U2 - 10.1182/blood-2013-07-511683

DO - 10.1182/blood-2013-07-511683

M3 - Journal article

C2 - 24516045

VL - 123

SP - 2389

EP - 2400

JO - Blood

JF - Blood

SN - 0006-4971

IS - 15

ER -

ID: 42873431