The RING finger protein Siah-1 regulates the level of the transcriptional coactivator OBF-1

The transcriptional coactivator OBF‐1, which interacts with Oct‐1 and Oct‐2 and the octamer site DNA, has been shown to be critical for development of a normal immune response and the formation of germinal centers in secondary lymphoid organs. Here we have identified the RING finger protein Siah‐1 as a protein interacting specifically with OBF‐1. This interaction is mediated by the C‐terminal part of Siah‐1 and by residues in the N‐terminus of OBF‐1, partly distinct from the residues required for formation of a complex with the Oct POU domains and the DNA. Interaction between Siah‐1 and OBF‐1 leads to downregulation of OBF‐1 protein level but not mRNA, and to a corresponding reduction in octamer site‐dependent transcription activation. Inhibition of the ubiquitin‐proteasome pathway in B cells leads to elevated levels of OBF‐1 protein. Furthermore, in immunized mice, OBF‐1 protein amounts are dramatically increased in primary activated B cells, without concomitant increase in OBF‐1 mRNA. These data suggest that Siah‐1 is part of a novel regulatory loop controlling the level of OBF‐1 protein in B cells.