HMGB1 inhibits cell death in yeast and mammalian cells and is abundantly expressed in human breast carcinoma

SPECIFIC AIMWe used a functional yeast survival screen in S. pombe to select for new anti-apoptotic mammalian genes. We present evidence that one of the genes we identified (HMGB1) is able to suppress cell death induced by the proapoptotic Bcl-2 family member Bak in yeast and to protect against apoptosis initiated by different stimuli in mammalian cells. We show high HMGB1 protein levels in human primary breast carcinoma and reduced Hmgb1 mRNA amounts in the lactating and involuting mouse mammary gland. These data suggest that HMGB1 may participate in the regulation of mammary gland apoptosis and that strong HMGB1 expression might promote tumor growth because of its anti-apoptotic properties.PRINCIPAL FINDINGS1. High mobility group-1 protein (HMGB1) protects against Bak-induced cell death in S. pombeWe used an inducible Bak expression system in S. pombe to screen a cDNA library for new anti-apoptotic mammalian genes. One of the S. pombe colonies surviving Bak expression after library transformation contai...