Clone pAT 133 identifies a gene that encodes another human member of a class of growth factor-induced genes with almost identical zinc-finger domains

Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10079-83. doi: 10.1073/pnas.88.22.10079.

Abstract

We report the structure and regulation of a gene represented by clone pAT 133, which is induced upon transition from a resting state (G0) through the early phase of the cell cycle (G1). The pAT 133 gene is immediately induced, with FOS-like kinetics, in human T cells and in fibroblasts. Primary structure analysis showed that the encoded protein contains three tandem zinc-finger sequences of the type Cys2-Xaa12-His2. This zinc-finger region, which is thought to bind DNA in a sequence-specific manner, is similar (greater than 80% on the amino acid level) to two previously described transcription factors pAT 225/EGR1 and pAT 591/EGR2. Except for the conserved zinc-finger domains, the amino acid sequences of the three proteins are distinct. This structural similarity suggests that the pAT 133 gene encodes a transcription factor with a specific biological function. Comparing the regulation of these related zinc-finger-encoding genes showed coordinate induction upon mitogenic stimulation of resting T lymphocytes and of resting fibroblasts. However, upon transition from a proliferating (G1) to a resting state of the cell cycle the three genes were differently regulated. In human histiocytic U937 cells mRNA of clone pAT 133 was constitutively expressed, whereas mRNA of pAT 225/EGR1 was induced upon induction of terminal differentiation. In contrast mRNA representing pAT 591/EGR2 was not expressed in these cells. This difference in gene regulation suggests distinct biological roles in the control of cell proliferation for the respective proteins.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cell Cycle
  • Cell Line
  • Cells, Cultured
  • Cloning, Molecular / methods
  • DNA / genetics
  • DNA / isolation & purification
  • Gene Expression Regulation
  • Gene Library
  • Genes*
  • Humans
  • Kidney Neoplasms / genetics
  • Lymphocyte Activation
  • Molecular Sequence Data
  • Plasmids*
  • Protein Conformation
  • RNA Splicing
  • RNA, Messenger / genetics
  • Sequence Homology, Nucleic Acid
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology*
  • Transcription Factors / metabolism
  • Wilms Tumor / genetics
  • Zinc Fingers / genetics*

Substances

  • RNA, Messenger
  • Transcription Factors
  • DNA

Associated data

  • GENBANK/M80632
  • GENBANK/S65590
  • GENBANK/S65595
  • GENBANK/S65622
  • GENBANK/X55687
  • GENBANK/X55688
  • GENBANK/X55689
  • GENBANK/X55690
  • GENBANK/X56856
  • GENBANK/X58180
  • GENBANK/X60104