Characterization of human NLZ1/ZNF703 identifies conserved domains essential for proper subcellular localization and transcriptional repression

J Cell Biochem. 2013 Jan;114(1):120-33. doi: 10.1002/jcb.24309.

Abstract

NET family members have recently emerged as important players in the development of multiple structures, from the trachea of fly larvae to the vertebrate eye and human breast cancers. However, their mechanisms of action are still poorly understood, and we lack a detailed characterization of their functional domains, as well as gene expression patterns-particularly in adult mammals. Here, we present a characterization of human NLZ1/ZNF703 (NocA-like zinc finger 1/Zinc finger 703), one of the two human NET family member genes. We show that the gene is ubiquitously expressed in adult human and mouse tissues, that three mRNA species with the same coding sequence are generated by alternative polyadenylation, and that the encoded protein contains six evolutionarily conserved domains, three of which are specific to NET proteins. Finally, we present functional evidence that these domains are necessary for proper subcellular distribution of and transcription repression by the NLZ1 protein, but not for its interaction with Groucho family co-repressors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Nucleus / metabolism
  • Conserved Sequence
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mice
  • Molecular Sequence Data
  • Polyadenylation*
  • Protein Structure, Tertiary
  • Protein Transport
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Transcription, Genetic

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • RNA, Messenger
  • Repressor Proteins
  • ZNF703 protein, human
  • Zeppo1 protein, mouse