An initial biochemical and cell biological characterization of the mammalian homologue of a central plant developmental switch, COP1

BMC Cell Biol. 2002 Dec 4;3:30. doi: 10.1186/1471-2121-3-30. Epub 2002 Dec 4.

Abstract

Background: Constitutive photomorphogenic 1 (COP1) has been defined as a central regulator of photomorphogenic development in plants, which targets key transcription factors for proteasome-dependent degradation. Although COP1 mammalian homologue has been previously reported, its function and distribution in animal kingdom are not known.

Results: Here we report the characterization of full-length human and mouse COP1 cDNAs and the genomic structures of the COP1 genes from several different species. Mammalian COP1 protein binds to ubiquitinated proteins in vivo and is itself ubiquitinated. Furthermore, mammalian COP1 is predominantly nuclear localized and exists primarily as a complex of over 700 kDa. Through mutagenesis studies, we have defined a leucine-rich nuclear export signal (NES) within the coiled-coil domain of mammalian COP1 and a nuclear localization signal (NLS), which is composed of two clusters of positive-charged amino acids, bridged by the RING finger. Disruption of the RING finger structure abolishes the nuclear import, while deletion of the entire RING finger restores the nuclear import.

Conclusions: Our data suggest that mammalian COP1, similar to its plant homologue, may play a role in ubiquitination. Mammalian COP1 contains a classic leucine-rich NES and a novel bipartite NLS bridged by a RING finger domain. We propose a working model in which the COP1 RING finger functions as a structural scaffold to bring two clusters of positive-charged residues within spatial proximity to mimic a bipartite NLS. Therefore, in addition to its well-characterized role in ubiquitination, the RING finger domain may also play a structural role in nuclear import.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Arabidopsis Proteins / chemistry
  • Arabidopsis Proteins / genetics
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Cytoplasm / chemistry
  • DNA, Complementary / chemistry
  • DNA, Complementary / genetics
  • Evolution, Molecular
  • Humans
  • Macromolecular Substances
  • Mice
  • Molecular Sequence Data
  • Nuclear Envelope / chemistry
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / genetics
  • Nucleic Acid Conformation
  • Plant Proteins / chemistry
  • Plant Proteins / genetics
  • Protein Sorting Signals / genetics
  • Protein Structure, Quaternary / genetics
  • Proteins / chemistry*
  • Proteins / genetics
  • Sequence Homology, Nucleic Acid*
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases*

Substances

  • Arabidopsis Proteins
  • Carrier Proteins
  • DNA, Complementary
  • Macromolecular Substances
  • Nuclear Proteins
  • Plant Proteins
  • Protein Sorting Signals
  • Proteins
  • Ubiquitin
  • AT2G32950 protein, Arabidopsis
  • COP1 protein, human
  • COP1 protein, mouse
  • Ubiquitin-Protein Ligases

Associated data

  • GENBANK/BK000438