Transcription Factors Activation by Alkaline pH

The pacC transcription factor is activated by alkaline pH conditions in the mold Aspergillus by activation of the pal pathway. Growth of wild-type Aspergillus in alkaline pH results in the proteolytic cleavage of the COOH-terminus of pacC; however, full-length, as well as the proteolytically cleaved form, of pacC is able to bind DNA. Mingot et al. studied how pH regulates pacC subcellular localization using pacC mutants, pal mutants, and pacC-green fluorescent fusion proteins. In the wild-type mold, cleaved pacC is formed in response to high pH and is completely redistributed to the nucleus. It is surprising that full-length pacC could also be detected in the nucleus. PacC undergoes a conformational change under alkaline conditions (from "closed" to "open") that requires the pal signaling pathway. This conformational change promotes the proteolytic processing of pacC. Using mutants of pacC, the authors showed that full-length pacC that can undergo this conformational change is able to target the nucleus without being cleaved. Increased pH may lead to the formation of two forms of pacC: the active cleaved pacC and the open conformation full-length pacC, both of which can bind to the consensus pacC recognition sites. It remains unclear whether the small amount of the full-length nuclear pacC is also an important transcriptional regulator.

J. M. Mingot, E. A. Espeso, E. Díez, M. A. Peñalva, Ambient pH signaling regulates nuclear localization of the Aspergillus nidulans PacC transcription factor. Mol. Cell. Biol. 21, 1688-1699 (2001). [Abstract] [Full Text]