Disease relevance of FPR4

• In the yeast Saccharomyces cerevisiae, an unusual complex of Hsp70 and J-type chaperones associates with ribosome-bound nascent chains, whereas in Escherichia coli the ribosome-associated peptidyl-prolyl-cis-trans isomerase, trigger factor, plays a predominant role [1].

High impact information on FPR4

• These results suggest that the conformational state of P38, controlled by Fpr4, is important for methylation of H3K36 by Set2 [2].
• The Ess1/Pin1 peptidyl-prolyl isomerase (PPIase) is thought to control mitosis by binding to cell cycle regulatory proteins and altering their activity [3].
• These PPIases consist of an NH(2)-terminal WW domain that binds to specific phosphoserine- or phosphothreonine-proline motifs present in a subset of phosphoproteins and a COOH-terminal PPIase domain that specifically isomerizes the phosphorylated serine/threonine-proline peptide bonds [4].
• Thus, partial unfolding of the active site of the parvulins was thought to be the cause of the deterioration of PPIase activity [5].
• Genes encoding the peptidyl proline isomerases Fpr3p and Fpr4p, when present on multicopy plasmids, will suppress this temperature-sensitive growth phenotype [6].

Biological context of FPR4

• Consistent with such an antagonistic role, abrogation of Fpr4 catalytic activity in vivo results in increased levels of H3K36 methylation and delayed transcriptional induction kinetics of specific genes in yeast [2].

Associations of FPR4 with chemical compounds

• Interestingly, the peptidyl proline isomerase domains of Fpr3p and Fpr4p are not required for suppression; rather the essential sequences include about 170 highly conserved residues at the proteins' N-termini [6].

References