A Lin-9 complex is recruited by B-Myb to activate transcription of G2/M genes in undifferentiated embryonal carcinoma cells

Research output: Contribution to journalArticle

Authors

Colleges, School and Institutes

Abstract

It has recently been discovered that cell-cycle gene transcription is regulated by a core complex named LINC that switches from a transcriptionally repressive complex in G0–G1 with the p130 or p107 pocket proteins and E2F4 to a transcriptionally active complex in S–G2 containing B-Myb. We have studied the function of LINC in F9 embryonal carcinoma cells, which are distinguished by a rapid cell cycle resulting from an extremely short G1 phase. We show that suppressing expression of the LINC component, Lin-9, in F9 cells causes arrest in mitosis, and we have used this system to screen for transcriptional targets. In these cells, B-Myb was found in complexes with Lin-9 and several other LINC constituents, however, the pocket proteins did not associate with LINC unless F9 cells were differentiated. Lin-9 and B-Myb were both required for transcription of G2/M genes such as Cyclin B1 and Survivin. Moreover, B-Myb was demonstrated to recruit Lin-9 to the Survivin promoter through multiple Myb-binding sites. The demonstration that a B-Myb/LINC complex is vital for progression through mitosis in cells lacking a G1/S checkpoint has implications for both undifferentiated embryonal cells and for cancers in which pocket protein function is compromised.

Details

Original languageEnglish
Pages (from-to)1737-1747
JournalOncogene
Volume28
Issue number15
Publication statusPublished - 16 Apr 2009