Developmental regulation of CRD-BP, an RNA-binding protein that stabilizes c-myc mRNA in vitro

Peter Leeds, Betsy T. Kren, Joan M. Boylan, Natalie A. Betz, Clifford J Steer, Philip A. Gruppuso, Jeffrey Ross

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

We previously isolated and characterized a coding region determinant-binding protein (CRD-BP) that might regulate c-myc mRNA post-transcriptionally. CRD-BP binds specifically to the coding region of c-myc mRNA and might stabilize c-myc mRNA in vitro by protecting it from endonucleolytic cleavage. Since c-myc abundance is regulated during embryonic development and cell replication, we investigated whether CRD-BP is also regulated in animal tissues. We focused on CRD-BP expression during rat liver development and liver regeneration, because c-myc mRNA is regulated post-transcriptionally in both cases. CRD-BP expression parallels c-myc expression during liver development; the protein is present in fetal and neonatal liver but is absent or in low abundance in adult liver. In contrast, the up-regulation of c-myc mRNA following partial hepatectomy is not accompanied by upregulation of CRD-BP. To our knowledge, CRD-BP is the first example of a putative mammalian mRNA-binding protein that is abundant in a fetal tissue but either absent from or scarce in adult tissues. Its expression in fetal liver and in transformed cell lines suggests CRD-BP is an oncofetal protein.

Original languageEnglish (US)
Pages (from-to)1279-1286
Number of pages8
JournalOncogene
Volume14
Issue number11
DOIs
StatePublished - 1997

Bibliographical note

Funding Information:
We thank Alan Poland and Ed Glover for their generous gift of hsp90 antiserum. This work was supported by Public Health Service grants CA63676 and CA07175 (to JR), HD24455 and HD11343 (to PAG), and DK-44649 (to CJS) from the National Institutes of Health. PL was the recipient of an American Cancer Society postdoctoral grant (PF-3870).

Keywords

  • Coding region determinant
  • Fetal development
  • mRNA stability

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