A functional SUMO-interacting motif in the transactivation domain of c-Myb regulates its myeloid transforming ability

Saether, T., Pattabiraman, D. R., Alm-Kristiansen, A. H., Vogt-Kielland, L. T., Gonda, T. J. and Gabrielsen, O. S. (2011) A functional SUMO-interacting motif in the transactivation domain of c-Myb regulates its myeloid transforming ability. Oncogene, 30 2: 212-222. doi:10.1038/onc.2010.397

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Author Saether, T.
Pattabiraman, D. R.
Alm-Kristiansen, A. H.
Vogt-Kielland, L. T.
Gonda, T. J.
Gabrielsen, O. S.
Title A functional SUMO-interacting motif in the transactivation domain of c-Myb regulates its myeloid transforming ability
Journal name Oncogene   Check publisher's open access policy
ISSN 0950-9232
Publication date 2011-01-13
Year available 2010
Sub-type Article (original research)
DOI 10.1038/onc.2010.397
Open Access Status File (Author Post-print)
Volume 30
Issue 2
Start page 212
End page 222
Total pages 11
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2011
Language eng
Abstract c-Myb is an essential hematopoietic transcription factor that controls proliferation and differentiation of progenitors during blood cell development. Whereas sumoylation of the C-terminal regulatory domain (CRD) is known to have a major impact on the activity of c-Myb, no role for noncovalent binding of small ubiquitin-like modifier (SUMO) to c-Myb has been described. Based on the consensus SUMO-interacting motif (SIM), we identified and examined putative SIMs in human c-Myb. Interaction and reporter assays showed that the SIM in the in the transactivation domain of c-Myb (V 267 NIV) is functional. This motif is necessary for c-Myb to be able to interact noncovalently with SUMO, preferentially SUMO2/3. Destroying the SUMO-binding properties by mutation resulted in a large increase in the transactivation potential of c-Myb. Mutational analysis and overexpression of conjugation-defective SUMO argued against intramolecular repression caused by sumoylated CRD and in favor of SUMO-dependent repression in trans. Using both a myeloid cell line-based assay and a primary hematopoietic cell assay, we addressed the transforming abilities of SUMO binding and conjugation mutants. Interestingly, only loss of SUMO binding, and not SUMO conjugation, enhanced the myeloid transformational potential of c-Myb. c-Myb with the SIM mutated conferred a higher proliferative ability than the wild-type and caused an effective differentiation block. This establishes SUMO binding as a mechanism involved in modulating the transactivation activity of c-Myb, and responsible for keeping the transforming potential of the oncoprotein in check.
Keyword c-Myb
SUMO-interacting motif
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 30 August 2010.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 24 Feb 2011, 13:34:37 EST by Kylie Hengst on behalf of UQ Diamantina Institute