Role of ubiquitin-like proteins in transcriptional regulation

Conjugation of ubiquitin-like proteins (Ubls) to components of the transcriptional machinery represents an important mechanism to allow switching between different activity states. While ubiquitin modification of transcription factors is associated with transcriptional activation, SUMO modification of transcription factors is most often associated with transcriptional repression. Recent experiments indicate that another Ubl, NEDD8, can also influence transcription. One of the characteristics of Uhl modification is that the biological consequences of conjugation do not appear proportionate to the small fraction of substrate that is modified. The low steady state levels of Ubl-modified substrates can be attributed to a highly dynamic situation in which proteins are conjugated to a particular Uhl only for the modification to be removed by Ubl-specific proteases. It therefore appears that an unmodified protein with a history of Uhl modification may have different properties from a protein that never has been modified. Here the diverse effects of Ubl modification are discussed and models proposed to explain Ubl actions.