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Puma and to a lesser extent Noxa are suppressors of Myc-induced lymphomagenesis

Puma and to a lesser extent Noxa are suppressors of Myc-induced lymphomagenesis
Puma and to a lesser extent Noxa are suppressors of Myc-induced lymphomagenesis
Evasion of apoptosis contributes importantly to c-Myc-induced tumorigenesis. The BH3-only Bcl-2 family members Puma and Noxa are critical pro-apoptotic transcriptional targets of p53, a major mediator of Myc-induced apoptosis and suppressor of Myc-induced tumorigenesis. Hence, we have explored the impact of their individual or combined loss on myc-driven lymphomagenesis. Notably, Puma deficiency both increased B-lineage cells and accelerated the development of B lymphoma, accompanied by leukaemia, but not of pre-B lymphoma. Noxa deficiency alone also increased B-lineage cells but did not accelerate lymphomagenesis. However, its deficiency combined with loss of one puma allele produced more rapid onset of both pre-B and B lymphomas than did loss of a single puma allele alone. Nevertheless, the acceleration evoked by loss of both genes was not as marked as that caused by p53 heterozygosity. These results show that Puma imposes a significant, and Noxa a minor barrier to c-Myc-driven lymphomagenesis. They also indicate that additional BH3-only proteins probably also drive Myc-induced apoptosis and that non-apoptotic functions of p53 may contribute substantially to its tumour suppressor role.
apoptosis, p53, Puma, Noxa, tumour suppressor
1350-9047
684-696
Michalak, E.M.
744b1922-454a-41f6-bec9-cdd4a3072e14
Jansen, E.S.
857a7894-190a-4fd5-91d3-a3bed7f53309
Happo, L.
bc4c68ba-ec79-48a8-9416-7a499063129f
Cragg, M.S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Tai, L.
0756eb21-c693-497c-af90-211741d4340c
Smyth, G.K.
2bfc3c84-3ce9-44c2-b438-2f13155760ac
Strasser, A.
2fe265c2-1bd2-401a-836e-e4c13ef2a188
Adams, J.M.
02a82914-102e-4e15-8a9f-cc9031a392f3
Scott, C.L.
a3670564-5617-494f-8386-ecee53f76086
Michalak, E.M.
744b1922-454a-41f6-bec9-cdd4a3072e14
Jansen, E.S.
857a7894-190a-4fd5-91d3-a3bed7f53309
Happo, L.
bc4c68ba-ec79-48a8-9416-7a499063129f
Cragg, M.S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Tai, L.
0756eb21-c693-497c-af90-211741d4340c
Smyth, G.K.
2bfc3c84-3ce9-44c2-b438-2f13155760ac
Strasser, A.
2fe265c2-1bd2-401a-836e-e4c13ef2a188
Adams, J.M.
02a82914-102e-4e15-8a9f-cc9031a392f3
Scott, C.L.
a3670564-5617-494f-8386-ecee53f76086

Michalak, E.M., Jansen, E.S., Happo, L., Cragg, M.S., Tai, L., Smyth, G.K., Strasser, A., Adams, J.M. and Scott, C.L. (2009) Puma and to a lesser extent Noxa are suppressors of Myc-induced lymphomagenesis. Cell Death and Differentiation, 16, 684-696. (doi:10.1038/cdd.2008.195).

Record type: Article

Abstract

Evasion of apoptosis contributes importantly to c-Myc-induced tumorigenesis. The BH3-only Bcl-2 family members Puma and Noxa are critical pro-apoptotic transcriptional targets of p53, a major mediator of Myc-induced apoptosis and suppressor of Myc-induced tumorigenesis. Hence, we have explored the impact of their individual or combined loss on myc-driven lymphomagenesis. Notably, Puma deficiency both increased B-lineage cells and accelerated the development of B lymphoma, accompanied by leukaemia, but not of pre-B lymphoma. Noxa deficiency alone also increased B-lineage cells but did not accelerate lymphomagenesis. However, its deficiency combined with loss of one puma allele produced more rapid onset of both pre-B and B lymphomas than did loss of a single puma allele alone. Nevertheless, the acceleration evoked by loss of both genes was not as marked as that caused by p53 heterozygosity. These results show that Puma imposes a significant, and Noxa a minor barrier to c-Myc-driven lymphomagenesis. They also indicate that additional BH3-only proteins probably also drive Myc-induced apoptosis and that non-apoptotic functions of p53 may contribute substantially to its tumour suppressor role.

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More information

Published date: 16 January 2009
Keywords: apoptosis, p53, Puma, Noxa, tumour suppressor

Identifiers

Local EPrints ID: 149053
URI: http://eprints.soton.ac.uk/id/eprint/149053
ISSN: 1350-9047
PURE UUID: ef936e1a-4ac2-49a9-8083-b66f6725e205
ORCID for M.S. Cragg: ORCID iD orcid.org/0000-0003-2077-089X

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Date deposited: 29 Apr 2010 14:50
Last modified: 14 Mar 2024 02:41

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Contributors

Author: E.M. Michalak
Author: E.S. Jansen
Author: L. Happo
Author: M.S. Cragg ORCID iD
Author: L. Tai
Author: G.K. Smyth
Author: A. Strasser
Author: J.M. Adams
Author: C.L. Scott

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