University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Program in Molecular Medicine

Publication Date

2013-1

Document Type

Article

Subjects

Animals; Female; HEK293 Cells; Humans; Oocytes; Peptidylprolyl Isomerase; Phosphorylation; Progesterone; Transcription Factors; Xenopus Proteins; mRNA Cleavage and Polyadenylation Factors

Disciplines

Amino Acids, Peptides, and Proteins | Cell Biology | Molecular Biology | Molecular Genetics | Nucleic Acids, Nucleotides, and Nucleosides

Abstract

Cytoplasmic polyadenylation is a conserved mechanism that controls mRNA translation and stability. A key protein that promotes polyadenylation-induced translation of mRNAs in maturing Xenopus oocytes is the cytoplasmic polyadenylation element binding protein (CPEB). During this meiotic transition, CPEB is subjected to phosphorylation-dependent ubiquitination and partial destruction, which is necessary for successive waves of polyadenylation of distinct mRNAs. Here we identify the peptidyl-prolyl cis-trans isomerase Pin1 as an important factor mediating CPEB destruction. Pin1 interacts with CPEB in an unusual manner in which it occurs prior to CPEB phosphorylation and prior to Pin1 activation by serine 71 dephosphorylation. Upon induction of maturation, CPEB becomes phosphorylated, which occurs simultaneously with Pin1 dephosphorylation. At this time, the CPEB-Pin1 interaction requires cdk1-catalyzed CPEB phosphorylation on S/T-P motifs. Subsequent CPEB ubiquitination and destruction are mediated by a conformational change induced by Pin1 isomerization of CPEB. Similar to M phase progression in maturing Xenopus oocytes, the destruction of CPEB during the mammalian cell cycle requires Pin1 as well. These data identify Pin1 as a new and essential factor regulating CPEB degradation.

Rights and Permissions

Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.

DOI of Published Version

10.1128/MCB.00904-12

Source

Mol Cell Biol. 2013 Jan;33(1):48-58. doi: 10.1128/MCB.00904-12. Epub 2012 Oct 22. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Molecular and cellular biology

PubMed ID

23090969

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