PUBLICATION

UHRF1 phosphorylation by Cyclin A2/CDK2 is required for zebrafish embryogenesis

Authors
Chu, J., Loughlin, E.A., Gaur, N.A., Senbanerjee, S., Jacob, V., Monson, C., Kent, B., Oranu, A., Ding, Y., Ukomadu, C., and Sadler, K.C.
ID
ZDB-PUB-111117-46
Date
2012
Source
Molecular biology of the cell   23(1): 59-70 (Journal)
Registered Authors
Chu, Jaime, Jacob, Vinitha, Monson, Christopher, Sadler Edepli, Kirsten C.
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Consensus Sequence
  • Cyclin A2/genetics
  • Cyclin A2/metabolism*
  • Cyclin-Dependent Kinase 2/metabolism*
  • Embryo, Nonmammalian/anatomy & histology
  • Embryonic Development*
  • Gastrula/embryology
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Structure, Tertiary
  • Protein Transport
  • Trans-Activators/chemistry
  • Trans-Activators/genetics
  • Trans-Activators/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
22072796 Full text @ Mol. Biol. Cell
Abstract

Ubiquitin-like, containing PHD and RING finger domains 1 (uhrf1) is regulated at the transcriptional level during the cell cycle and in developing zebrafish embryos. We identify phosphorylation as a novel means of regulating UHRF1 and demonstrate that Uhrf1 phosphorylation is required for gastrulation in zebrafish. Human UHRF1 contains a conserved cyclin dependent kinase 2 (CDK2) phosphorylation site at serine 661 that is phosphorylated in vitro by CDK2 partnered with Cyclin A2 (CCNA2), but not Cyclin E. A phosphoserine-661 specific antibody recognizes UHRF1 in both in mammalian cancer cells and in non-transformed zebrafish cells, but not in zebrafish bearing a mutation in ccna2. Depleting Uhrf1 from zebrafish embryos by morpholino injection causes arrest before gastrulation and early embryonic death. This phenotype is rescued by wild-type UHRF1, but not by UHRF1 in which the phospho-acceptor site is mutated, demonstrating that UHRF1 phosphorylation is essential for embryogenesis. UHRF1 was detected in the nucleus and cytoplasm, whereas non-phosphorylatable UHRF1 is unable to localize to the cytoplasm, suggesting the importance of localization in UHRF1 function. Together, these data point to an essential role for UHRF1 phosphorylation by CDK/CCNA2 during early vertebrate development.

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