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The presence of C/EBPα and its degradation are both required for TRIB2-mediated leukaemia

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Harvard

O'Connor, C, Lohan, F, Campos, J, Ohlsson, E, Salomè, M, Forde, C, Artschwager, R, Liskamp, RM, Cahill, MR, Kiely, PA, Porse, B & Keeshan, K 2016, 'The presence of C/EBPα and its degradation are both required for TRIB2-mediated leukaemia' Oncogene, bind 35, nr. 40, s. 5272-5281. https://doi.org/10.1038/onc.2016.66

APA

O'Connor, C., Lohan, F., Campos, J., Ohlsson, E., Salomè, M., Forde, C., ... Keeshan, K. (2016). The presence of C/EBPα and its degradation are both required for TRIB2-mediated leukaemia. Oncogene, 35(40), 5272-5281. https://doi.org/10.1038/onc.2016.66

CBE

O'Connor C, Lohan F, Campos J, Ohlsson E, Salomè M, Forde C, Artschwager R, Liskamp RM, Cahill MR, Kiely PA, Porse B, Keeshan K. 2016. The presence of C/EBPα and its degradation are both required for TRIB2-mediated leukaemia. Oncogene. 35(40):5272-5281. https://doi.org/10.1038/onc.2016.66

MLA

Vancouver

Author

O'Connor, C ; Lohan, F ; Campos, J ; Ohlsson, E ; Salomè, M ; Forde, C ; Artschwager, R ; Liskamp, R M ; Cahill, M R ; Kiely, P A ; Porse, B ; Keeshan, K. / The presence of C/EBPα and its degradation are both required for TRIB2-mediated leukaemia. I: Oncogene. 2016 ; Bind 35, Nr. 40. s. 5272-5281.

Bibtex

@article{a9d7defaffb64a4585497206d1013b72,
title = "The presence of C/EBPα and its degradation are both required for TRIB2-mediated leukaemia",
abstract = "C/EBPα (p42 and p30 isoforms) is commonly dysregulated in cancer via the action of oncogenes, and specifically in acute myeloid leukaemia (AML) by mutation. Elevated TRIB2 leads to the degradation of C/EBPα p42, leaving p30 intact in AML. Whether this relationship is a cooperative event in AML transformation is not known and the molecular mechanism involved remains elusive. Using mouse genetics, our data reveal that in the complete absence of C/EBPα, TRIB2 was unable to induce AML. Only in the presence of C/EBPα p42 and p30, were TRIB2 and p30 able to cooperate to decrease the latency of disease. We demonstrate that the molecular mechanism involved in the degradation of C/EBPα p42 requires site-specific direct interaction between TRIB2 and C/EBPα p42 for the K48-specific ubiquitin-dependent proteasomal degradation of C/EBPα p42. This interaction and ubiquitination is dependent on a critical C terminal lysine residue on C/EBPα. We show effective targeting of this pathway pharmacologically using proteasome inhibitors in TRIB2-positive AML cells. Together, our data show that excess p30 cooperated with TRIB2 only in the presence of p42 to accelerate AML, and the direct interaction and degradation of C/EBPα p42 is required for TRIB2-mediated AML.Oncogene advance online publication, 21 March 2016; doi:10.1038/onc.2016.66.",
author = "C O'Connor and F Lohan and J Campos and E Ohlsson and M Salom{\`e} and C Forde and R Artschwager and Liskamp, {R M} and Cahill, {M R} and Kiely, {P A} and B Porse and K Keeshan",
year = "2016",
month = "3",
day = "21",
doi = "10.1038/onc.2016.66",
language = "English",
volume = "35",
pages = "5272--5281",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "40",

}

RIS

TY - JOUR

T1 - The presence of C/EBPα and its degradation are both required for TRIB2-mediated leukaemia

AU - O'Connor, C

AU - Lohan, F

AU - Campos, J

AU - Ohlsson, E

AU - Salomè, M

AU - Forde, C

AU - Artschwager, R

AU - Liskamp, R M

AU - Cahill, M R

AU - Kiely, P A

AU - Porse, B

AU - Keeshan, K

PY - 2016/3/21

Y1 - 2016/3/21

N2 - C/EBPα (p42 and p30 isoforms) is commonly dysregulated in cancer via the action of oncogenes, and specifically in acute myeloid leukaemia (AML) by mutation. Elevated TRIB2 leads to the degradation of C/EBPα p42, leaving p30 intact in AML. Whether this relationship is a cooperative event in AML transformation is not known and the molecular mechanism involved remains elusive. Using mouse genetics, our data reveal that in the complete absence of C/EBPα, TRIB2 was unable to induce AML. Only in the presence of C/EBPα p42 and p30, were TRIB2 and p30 able to cooperate to decrease the latency of disease. We demonstrate that the molecular mechanism involved in the degradation of C/EBPα p42 requires site-specific direct interaction between TRIB2 and C/EBPα p42 for the K48-specific ubiquitin-dependent proteasomal degradation of C/EBPα p42. This interaction and ubiquitination is dependent on a critical C terminal lysine residue on C/EBPα. We show effective targeting of this pathway pharmacologically using proteasome inhibitors in TRIB2-positive AML cells. Together, our data show that excess p30 cooperated with TRIB2 only in the presence of p42 to accelerate AML, and the direct interaction and degradation of C/EBPα p42 is required for TRIB2-mediated AML.Oncogene advance online publication, 21 March 2016; doi:10.1038/onc.2016.66.

AB - C/EBPα (p42 and p30 isoforms) is commonly dysregulated in cancer via the action of oncogenes, and specifically in acute myeloid leukaemia (AML) by mutation. Elevated TRIB2 leads to the degradation of C/EBPα p42, leaving p30 intact in AML. Whether this relationship is a cooperative event in AML transformation is not known and the molecular mechanism involved remains elusive. Using mouse genetics, our data reveal that in the complete absence of C/EBPα, TRIB2 was unable to induce AML. Only in the presence of C/EBPα p42 and p30, were TRIB2 and p30 able to cooperate to decrease the latency of disease. We demonstrate that the molecular mechanism involved in the degradation of C/EBPα p42 requires site-specific direct interaction between TRIB2 and C/EBPα p42 for the K48-specific ubiquitin-dependent proteasomal degradation of C/EBPα p42. This interaction and ubiquitination is dependent on a critical C terminal lysine residue on C/EBPα. We show effective targeting of this pathway pharmacologically using proteasome inhibitors in TRIB2-positive AML cells. Together, our data show that excess p30 cooperated with TRIB2 only in the presence of p42 to accelerate AML, and the direct interaction and degradation of C/EBPα p42 is required for TRIB2-mediated AML.Oncogene advance online publication, 21 March 2016; doi:10.1038/onc.2016.66.

U2 - 10.1038/onc.2016.66

DO - 10.1038/onc.2016.66

M3 - Journal article

VL - 35

SP - 5272

EP - 5281

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 40

ER -

ID: 46359285