ZFIN ID: ZDB-PUB-111117-46
UHRF1 phosphorylation by Cyclin A2/CDK2 is required for zebrafish embryogenesis
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.
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

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.