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Mol. Cell. Biol., 01 1995, 120-128, Vol 15, No. 1
B Lecka-Czernik, CK Lumpkin Jr and S Goldstein
We carried out subtractive enrichment of a cDNA library derived from mRNA
of senescent human diploid fibroblasts (HDF) established from a subject
with Werner syndrome of premature aging. By differential screening, we
isolated an overexpressed cDNA sequence (S1-5) that codes for a novel
protein containing epidermal growth factor (EGF)-like domains which match
the EGF-like consensus sequences within several known extracellular
proteins that play a role in cell growth, development, and cell signalling.
S1-5 mRNA is overexpressed in Werner syndrome and senescent normal HDF, is
induced by growth arrest of young normal cells, but is significantly
decreased by high serum, conditions which promote cellular proliferation.
Paradoxically, microinjection into young HDF of two different lengths of
S1-5 mRNA, containing different putative AUG translational start sites,
consistently stimulated rather than inhibited DNA synthesis by an apparent
autocrine/paracrine mechanism. Thus, the S1-5 gene product may represent a
negative and/or positive factor whose ultimate activity is modulated by the
cell environment as occurs with other members of EGF- like family.
Copyright © 1995, American Society for Microbiology
An overexpressed gene transcript in senescent and quiescent human fibroblasts encoding a novel protein in the epidermal growth factor- like repeat family stimulates DNA synthesis
Department of Medicine, University of Arkansas for Medical Sciences, Little Rock.
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