Myb proteins: angels and demons in normal and transformed cells

Ye Zhou¹, Scott A. Ness¹

1Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131-0001 USA

TABLE OF CONTENTS

1. Abstract

2. Introduction

2.1. Significance of c-Myb in human disease

2.2. Features that make c-Myb unique

2.3. Questions to be addressed

3. The two faces of myb: a regulator and an oncogene

3.1. Myb as a critical regulator in normal cells

3.2. Myb unveiled becomes an oncogene

3.3. N-terminal deletions of c-Myb

3.4. C-terminal deletions affect intra- and intermolecular interactions

3.5. Wnt signaling and regulation of c-Myb stability

3.6. Structure and activities of the Myb DNA binding (SANT) domain

3.7. The related proteins, A-Myb and B-Myb, are not oncogenic

3.8. Mutations change the transcriptional activities of c-Myb

4. Does Myb regulate differentiation, proliferation or both?

4.1. Reversible regulation of differentiation by v-Myb

4.2. Myb target genes and transforming activities are lineage- and differentiation-specific

4.3. Myb is a key regulator of stem cell fate

4.4. Myb target genes may change during differentiation and the cell cycle

5. Mechanisms affecting c-Myb activity and specificity

5.1. Activation of the c-myb gene in tumors

5.2. Alternative RNA splicing as a novel mechanism for unleashing c-Myb oncogenicity

5.3.Regulation of c-Myb expression through microRNAs

6. Perspective

7. Acknowledgement

8. References

1. ABSTRACT