GSBS Student Publications

Title

Spatial regulation of beta-actin translation by Src-dependent phosphorylation of ZBP1

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology

Date

11-25-2005

Document Type

Article

Medical Subject Headings

Actins; Animals; Avian Proteins; Cell Line; *Cell Polarity; Chickens; DNA-Binding Proteins; Glycoproteins; Humans; Molecular Sequence Data; Phosphorylation; *Protein Biosynthesis; Proto-Oncogene Proteins pp60(c-src); RNA, Messenger; RNA, Small Interfering; RNA-Binding Proteins

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Localization of beta-actin messenger RNA to sites of active actin polymerization modulates cell migration during embryogenesis, differentiation and possibly carcinogenesis. This localization requires the oncofetal protein ZBP1 (Zipcode binding protein 1), which binds to a conserved 54-nucleotide element in the 3'-untranslated region of the beta-actin mRNA known as the 'zipcode'. ZBP1 promotes translocation of the beta-actin transcript to actin-rich protrusions in primary fibroblasts and neurons. It is not known how the ZBP1-RNA complex achieves asymmetric protein sorting by localizing beta-actin mRNA. Here we show that chicken ZBP1 modulates the translation of beta-actin mRNA. ZBP1 associates with the beta-actin transcript in the nucleus and prevents premature translation in the cytoplasm by blocking translation initiation. Translation only occurs when the ZBP1-RNA complex reaches its destination at the periphery of the cell. At the endpoint of mRNA transport, the protein kinase Src promotes translation by phosphorylating a key tyrosine residue in ZBP1 that is required for binding to RNA. These sequential events provide both temporal and spatial control over beta-actin mRNA translation, which is important for cell migration and neurite outgrowth.

Rights and Permissions

Citation: Nature. 2005 Nov 24;438(7067):512-5. Link to article on publisher's site

Related Resources

Link to article in PubMed

Journal Title

Nature

PubMed ID

16306994