| Autor: |
Shibanuma, Motoko, Mochizuki, Emi, Maniwa, Rika, Mashimo, Jun-Ichi, Nishiya, Naoyuki, Imai, Shin-Ichiro, Takano, Toshiya, Oshimura, Mitsuo, Nose, Kiyoshi |
| Zdroj: |
Molecular and Cellular Biology; March 1997, Vol. 17 Issue: 3 p1224-1235, 12p |
| Abstrakt: |
The hic-5gene encodes a novel protein with Zn finger-like (LIM) motifs, the expression of which increases during cellular senescence. The ectopic expression of hic-5in nontumorigenic immortalized human fibroblasts, whose expression levels of hic-5were significantly reduced in comparison with those of mortal cells, decreased colony-forming efficiency. Stable clones expressing high levels of hic-5mRNA 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-fosinducibility. Furthermore, these clones acquired a senescence-like phenotype, such as growth retardation; senescence-like morphology; and increased expression of Cip1/WAF1/sdi1after 20 to 40 population doublings. On the other hand, antisense RNA expression of hic-5in 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-5is 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. |
| Databáze: |
Supplemental Index |
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