Displaying an unprecedented dual role for a transcription factor, activating transcription factor 2 (ATF2) also responds to DNA damage, according to Ze'ev Ronai and colleagues at the Burnham Institute in La Jolla, Calif.
For its transcriptional regulatory roles, ATF2 is activated by phosphorylation via the JNK/p38 pathway. But alternate phosphorylation sites at serines 490 and 498 appear to be recognized by the kinase ataxia telangiectasia mutated (ATM). ATF2 phosphorylated at those serines localized at irradiation-induced double-strand break (DSB) repair foci. When the researchers inhibited JNK/p38 or disrupted transcriptional regulatory activity of ATF2, the protein continued to show up at these DSBs.1 Ronai's group found that in mammalian cells subjected to ionizing radiation, ATM phosphorylates ATF2, which plays an important role in the DSB repair process.
In recent years, mounting evidence has supported the idea that certain "moonlighting" proteins can perform multiple jobs. This paper demonstrates, however, that the two functions ...
