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PMID: 9032249 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Induction of senescence-like phenotypes by forced expression of hic-5, which encodes a novel LIM motif protein, in immortalized human fibroblasts.

Molecular and cellular biology ·Vol. 17 ·No. 3 ·1997-03-00 ·Pages 1224-35

Shibanuma M, Mochizuki E, Maniwa R, Mashimo J, Nishiya N, Imai S, Takano T, Oshimura M, Nose K

Abstract

The hic-5 gene encodes a novel protein with Zn finger-like (LIM) motifs, the expression of which increases during cellular senescence. The ectopic expression of hic-5 in nontumorigenic immortalized human fibroblasts, whose expression levels of hic-5 were significantly reduced in comparison with those of mortal cells, decreased colony-forming efficiency. Stable clones expressing high levels of hic-5 mRNA showed higher levels of mRNAs for several extracellular matrix-related proteins, along with the alteration of an alternative splicing as seen in senescent cells and decreased c-fos inducibility. Furthermore, these clones acquired a senescence-like phenotype, such as growth retardation; senescence-like morphology; and increased expression of Cip1/WAF1/sdi1 after 20 to 40 population doublings. On the other hand, antisense RNA expression of hic-5 in human normal diploid fibroblasts delayed the senescence process. HIC-5 was localized in nuclei and had affinity for DNA. Based on these observations, we speculated that HIC-5 affected the expression of senescence-related genes through interacting with DNA and thereby induced the senescence-like phenotypes. To our knowledge, hic-5 is the first single gene that could induce senescence-like phenotypes in a certain type of immortalized human cell and mediate the normal process of senescence.

MeSH Terms
Alternative Splicing Amino Acid Sequence Animals Cell Division Cell Line Cell Nucleus/chemistry Cellular Senescence/genetics Collagenases/genetics Cyclin-Dependent Kinase Inhibitor p21 Cyclins/genetics Cytoskeletal Proteins DNA/biosynthesis DNA-Binding Proteins/analysis,genetics Fibroblasts/cytology Fibronectins/genetics Gene Expression Genes, fos/genetics Humans Intracellular Signaling Peptides and Proteins LIM Domain Proteins Mice Molecular Sequence Data Phenotype RNA, Antisense/genetics RNA, Messenger/biosynthesis Zinc Fingers
Chemicals
CDKN1A protein, human Cdkn1a protein, mouse Cyclin-Dependent Kinase Inhibitor p21 Cyclins Cytoskeletal Proteins DNA-Binding Proteins Fibronectins Intracellular Signaling Peptides and Proteins LIM Domain Proteins RNA, Antisense RNA, Messenger TGFB1I1 protein, human Tgfb1i1 protein, mouse DNA Collagenases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Shibanuma M
Department of Microbiology, Showa University School of Pharmaceutical Sciences, Shinagawa-ku, Tokyo, Japan.
Mochizuki E
Maniwa R
Mashimo J
Nishiya N
Imai S
Takano T
Oshimura M
Nose K
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.17.3.1224
Published
1997-03-00
Pages
1224-35
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC231847
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.17.3.1224 PMC Full Text View journal details
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