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Trivedi, A.K.* ; Bararia, D.* ; Christopeit, M.* ; Peer Zada, A.A. ; Singh, S.M.* ; Kieser, A. ; Hiddemann, W.* ; Behre, H.M.* ; Behre, G.*

Proteomic identification of C/EBP-DBD multiprotein complex: JNK1 activates stem cell regulator C/EBPalpha by inhibiting its ubiquitination.

Oncogene 26, 1789-1801 (2007)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Functional inactivation of transcription factors in hematopoietic stem cell development is involved in the pathogenesis of acute myeloid leukemia (AML). Stem cell regulator C/enhancer binding protein (EBP)alpha is among such transcription factors known to be inactive in AML. This is either due to mutations or inhibition by protein-protein interactions. Here, we applied a mass spectrometry-based proteomic approach to systematically identify putative co-activator proteins interacting with the DNA-binding domain (DBD) of C/EBP transcription factors. In our proteomic screen, we identified c-Jun N-terminal kinase (JNK) 1 among others such as PAK6, MADP-1, calmodulin-like skin proteins and ZNF45 as proteins interacting with DBD of C/EBPs from nuclear extract of myelomonocytic U937 cells. We show that kinase JNK1 physically interacts with DBD of C/EBP alpha in vitro and in vivo. Furthermore, we show that active JNK1 inhibits ubiquitination of C/EBP alpha possibly by phosphorylating in its DBD. Consequently, JNK1 prolongs C/EBP alpha protein half-life leading to its enhanced transactivation and DNA-binding capacity. In certain AML patients, however, the JNK1 mRNA expression and its kinase activity is decreased which suggests a possible reason for C/EBP alpha inactivation in AML. Thus, we report the first proteomic screen of C/EBP-interacting proteins, which identifies JNK1 as positive regulator of C/EBP alpha.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter JNK1; C/EBPalpha; ubiquitination; AML and proteomics
ISSN (print) / ISBN 0950-9232
e-ISSN 0950-9232
Zeitschrift Oncogene
Quellenangaben Band: 26, Heft: 12, Seiten: 1789-1801 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Gene Vector (AGV)