Regulation of transcription factors by protein degradation

The level of transcription factors is tightly controlled by their rates of synthesis and degradation. Many critical factors are maintained at an appro priate level by targeted addition of ubiquitin and degradation via the prot easome. Whereas ubiquitination targets modified proteins for degradation, m odification of substrates by the family of ubiquitin-like proteins does not target the proteins for degradation but can alter the stability and other properties of the modified proteins. Here we discuss the elaborate mechanis ms that have evolved to allow specific recognition of substrates targeted f or modification. Specific examples are discussed to illustrate the differen t mechanisms involved and the importance of regulated degradation in diseas es such as cancer.