Temperature-dependent modification and activation of B-MYB: implications for cell survival.
B-MYB is a ubiquitous transcription factor with an essential role in mouse development. Because cells with a disrupted B-MYB gene cannot be obtained, it is still unknown what is the critical function(s) exerted by B-MYB in mammalian cells. In this study we have observed that reducing B-MYB expression in primary human fibroblasts by using RNA interference results in a partial block of the cells in the G(2) phase of the cell cycle and cell death. Surprisingly, suppressing B-MYB transcriptional activity with a dominant-negative molecule is without effect, suggesting that its transactivating function is not essential. Only human or murine fibroblasts exposed to high temperature are sensitized to cell death in the presence of dominant-negative B-MYB. This correlates with temperature-dependent binding of endogenous B-MYB to transcriptional regulatory elements of the stress-related gene ApoJ/clusterin. We find that regulation of ApoJ/clusterin by B-MYB is a pro-survival response to thermal stress. Thus, B-MYB is regulated by temperature to activate genes required for cell survival.
Santilli
Giorgia
G
Molecular Haematology and Cancer Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, United Kingdom.
Schwab
Rebekka
R
Watson
Roger
R
Ebert
Cathy
C
Aronow
Bruce J
BJ
Sala
Arturo
A
D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D016923:Cell Death / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D016195:G2 Phase / Q000235:genetics; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013696:Temperature; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C064352:MYBL2 protein, human; D034741:RNA, Small Interfering; D015534:Trans-Activators