Abstract
B-MYB, a highly conserved member of the MYB transcription factor family, is expressed ubiquitously in proliferating cells and plays key roles in important cell cycle-related processes, such as control of G2/M-phase transcription, cytokinesis, G1/S-phase progression and DNA-damage reponse. Deregulation of B-MYB function is characteristic of several types of tumor cells, underlining its oncogenic potential. To gain a better understanding of the functions of B-MYB we have employed affinity purification coupled to mass spectrometry to discover novel B-MYB interacting proteins. Here we have identified the zinc-finger proteins ZMYM2 and ZMYM4 as novel B-MYB binding proteins. ZMYM4 is a poorly studied protein whose initial characterization reported here shows that it is highly SUMOylated and that its interaction with B-MYB is stimulated upon induction of DNA damage. Unlike knockdown of B-MYB, which causes G2/M arrest and defective cytokinesis in HEK293 cells, knockdown of ZMYM2 or ZMYM4 have no obvious effects on the cell cycle of these cells. By contrast, knockdown of ZMYM2 strongly impaired the G1/S-phase progression of HepG2 cells, suggesting that ZMYM2, like B-MYB, is required for entry into S-phase in these cells. Overall, our work identifies two novel B-MYB binding partners with possible functions in the DNA-damage response and the G1/S-transition.
Highlights
B-MYB, a highly conserved member of the MYB transcription factor family, is expressed ubiquitously in proliferating cells and plays key roles in important cell cycle-related processes, such as control of G2/Mphase transcription, cytokinesis, G1/S-phase progression and DNA-damage reponse
This led to a list of proteins detected in three independent experiments in samples derived from GFP/B-MYB expressing cells but absent from samples derived form cells expressing only GFP (Supplementary Table S1)
zinc finger MYM-type protein 4 (ZMYM4) has been very poorly studied so far; apart from a single report showing that the ZMYM4 gene is overexpressed in a fraction of human lung adenocarcinomas and squamous cell carcinomas, suggesting that it might have a role in cancer development[33], virtually nothing is known about the function of ZMYM4
Summary
B-MYB, a highly conserved member of the MYB transcription factor family, is expressed ubiquitously in proliferating cells and plays key roles in important cell cycle-related processes, such as control of G2/Mphase transcription, cytokinesis, G1/S-phase progression and DNA-damage reponse. Our work identifies two novel B-MYB binding partners with possible functions in the DNA-damage response and the G1/S-transition. The highly conserved MYB proto-oncogene family member B-MYB is ubiquitously expressed in proliferating cells where it acts as an essential cell cycle-regulated transcription factor[1,2]. In the work reported here we have employed affinity-purification of a GFP-B-MYB fusion protein expressed in HEK293T cells in conjunction with mass spectrometry to explore the B-MYB interacting proteome and to better understand the complex functions of B-MYB. We have identified and characterized the zinc finger proteins ZMYM4 and ZMYM2 as novel B-MYB binding factors
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