Identification and characterization of a novel and functional murine Pin1 isoform.
Pin1, a phosphorylation-dependent peptidyl-prolyl cis/trans isomerase (PPIase), regulates the activity of a number of cell cycle regulators, transcription factors, and microtubule-associated tau. Aberrant expression of Pin1 is implicated in carcinogenesis and neurodegenerative diseases. Yet, there are discrepancies regarding its biological significance in different organisms. Pin1 was essential in HeLa cells, while Pin1-deficient mice showed no lethal phenotypes. We here identified a novel murine Pin1 isoform (mPin1L) consisting of the WW domain and the PPIase domain. Murine Pin1L shares 92% sequence identity with the wild-type Pin1 and shows wide tissue distribution with highest levels in mouse testis. The recombinant mPin1L is enzymatically active, but is approximately three times less efficient than Pin1 in catalyzing the cis/trans isomerization. These data suggest that mPin1L may serve as a surrogate for Pin1. The finding provides insights into phenotypic consequences for Pin1-null mice and may facilitate future biological study and pharmacological development in mice.
Zhu
Jeff X
JX
Department of Biochemical Pharmacology, Pfizer Global R&D, San Diego, CA 92121, USA. Jeff.Zhu@Pfizer.com
Dagostino
Eleanor
E
Rejto
Paul A
PA
Mroczkowski
Barbara
B
Murray
Brion
B
D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002384:Catalysis; D002875:Chromosomes / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D016415:Sequence Alignment; D013379:Substrate Specificity
D018076:DNA, Complementary; D007527:Isoenzymes; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010455:Peptides; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse