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.
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.
Müller
H J
HJ
Bernhard Nocht Institute for Tropical Medicine, Hamburg, Federal Republic of Germany.
Skerka
C
C
Bialonski
A
A
Zipfel
P F
PF
D000595:Amino Acid Sequence; D001483:Base Sequence; D002453:Cell Cycle; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular / Q000379:methods; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005786:Gene Expression Regulation; D015723:Gene Library; D005796:Genes; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010957:Plasmids; D011487:Protein Conformation; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D009396:Wilms Tumor / Q000235:genetics; D016335:Zinc Fingers / Q000235:genetics*
D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA