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Titolo:
Phosphorylation-dependent conformation and proteolytic stability of c-Myb
Autore:
Bies, J; Feikova, S; Markus, J; Wolff, L;
Indirizzi:
Slovak Acad Sci, Canc Res Inst, Mol Virol Lab, Bratislava 83392, Slovakia Slovak Acad Sci Bratislava Slovakia 83392 ab, Bratislava 83392, Slovakia NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892 Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA
Titolo Testata:
BLOOD CELLS MOLECULES AND DISEASES
fascicolo: 2, volume: 27, anno: 2001,
pagine: 422 - 428
SICI:
1079-9796(200103)27:2<422:PCAPSO>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
ONCOGENIC ACTIVATION; PROTEIN; SITE; DNA; DOMAIN;
Keywords:
c-Myb; phosphorylation; conformation; DNA-binding; proteolysis; 26S proteasome; Ser/Thr phosphatases;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
16
Recensione:
Indirizzi per estratti:
Indirizzo: Bies, J Slovak Acad Sci, Canc Res Inst, Mol Virol Lab, Bratislava 83392, Slovakia Slovak Acad Sci Bratislava Slovakia 83392 islava 83392, Slovakia
Citazione:
J. Bies et al., "Phosphorylation-dependent conformation and proteolytic stability of c-Myb", BL CELL M D, 27(2), 2001, pp. 422-428

Abstract

The c-Myb oncoprotein is a critical regulator of hematopoietic cell proliferation and differentiation. Normal c-Myb is rapidly degraded by the ubiquitin-26S proteasome pathway, and instability determinants have been localized within the negative regulatory domain in the carboxyl terminus. Our recent work has shown that, in myeloid cells, inhibition of cellular Ser/Thr protein phosphatases with okadaic acid (OA) causes a rapid increase in c-Myb phosphorylation and 26S proteasome-dependent breakdown [J. Bies, S. Feikova,D. P. Bottaro, and L. Wolff(2000) Oncogene 19, 2846-2854]. Furthermore, phosphoamino acid analyses revealed that the increase in phosphorylation was mainly on threonine residues. Here we investigated the ability of c-Myb to bind DNA following phosphorylation. Our results suggest that the hyperphosphorylated form of c-Myb binds to DNA with affinity very similar to the hypophosphorylated form. Therefore, the increased proteolytic instability of the former cannot be explained by a difference in DNA-binding capacity. Conformational changes in the carboxyl terminus were proposed previously to be aconsequence of phosphorylation because we observed phosphorylation-inducedalterations in gel electrophoresis mobilities and alterations in recognition by specific monoclonal antibodies. Further support for this notion has come from this study, in which we have detected new degradation products in electrophoretic mobility shift assays, as well as an increased rate of in vitro proteolysis, following OA treatment. We speculate that these alterations in the conformation of the negative regulatory domain expose epitopes onthe surface of c-Myb, which in turn can serve as recognition signal(s) forubiquitin-26S proteasome proteolytic machinery.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 19:16:14