Peptidyl-prolyl cis/trans isomerases and transcription: is there a twist in the tail?
Eukaryotic transcription is regulated predominantly by the post-translational modification of the participating components. One such modification is the cis-trans isomerization of peptidyl-prolyl bonds, which results in a conformational change in the protein involved. Enzymes that carry out this reaction include the yeast peptidyl-prolyl cis/trans isomerase Ess1 and its human counterpart Pin1, both of which recognize phosphorylated target motifs exclusively. Consequently, they operate together with proline-directed serine-threonine kinases and phosphatases. High-profile client proteins involved in transcription include steroid hormone receptors, cell-cycle regulators and immune mediators. Other key targets are elements of the transcription machinery, including the multiply phosphorylated carboxy-terminal domain of RNA polymerase II. Changes in isomerase activity have been shown to alter the transactivation potential, protein stability or intracellular localization of these client proteins. The resulting disruption to developmental processes and cell proliferation has been linked, in some cases, to human cancers.
Shaw
Peter E
PE
Centre for Biochemistry and Cell Biology (CBCB), School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK. peter.shaw@nottingham.ac.uk
D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007109:Immunity / Q000235:genetics; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012319:RNA Polymerase II / Q000378:metabolism; D011987:Receptors, Steroid / Q000737:chemistry / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D015003:Yeasts / Q000201:enzymology / Q000235:genetics
D018797:Cell Cycle Proteins; D016328:NF-kappa B; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D011987:Receptors, Steroid; D018808:Transcription Factor AP-1; D012319:RNA Polymerase II; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase