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Article
Open AccessDistinct functions of wild-type and R273H mutant Δ133p53α differentially regulate glioblastoma aggressiveness and therapy-induced senescence
Despite being mutated in 92% of TP53 mutant cancers, how mutations on p53 isoforms affect their activities remain largely unknown. Therefore, exploring the effect of mutations on p53 isoforms activities is a crit...
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Article
Open AccessEML4-ALK induces cellular senescence in mortal normal human cells and promotes anchorage-independent growth in hTERT-transduced normal human cells
Chromosomal inversions involving anaplastic lymphoma kinase (ALK) and echinoderm microtubule associated protein like 4 (EML4) generate a fusion protein EML4-ALK in non-small cell lung cancer (NSCLC). The understa...
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Article
Open AccessΔ133p53α, a natural p53 isoform, contributes to conditional reprogramming and long-term proliferation of primary epithelial cells
We previously developed the technique of conditional reprogramming (CR), which allows primary epithelial cells from fresh or cryopreserved specimens to be propagated long-term in vitro, while maintaining their...
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Article
p53 isoforms regulate premature aging in human cells
Cellular senescence is a hallmark of normal aging and aging-related syndromes, including the premature aging disorder Hutchinson-Gilford Progeria Syndrome (HGPS), a rare genetic disorder caused by a single mut...
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Article
Δ133p53 represses p53-inducible senescence genes and enhances the generation of human induced pluripotent stem cells
p53 functions to induce cellular senescence, which is incompatible with self-renewal of pluripotent stem cells such as induced pluripotent stem cells (iPSC) and embryonic stem cells (ESC). However, p53 also ha...
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Article
Autophagic degradation of the inhibitory p53 isoform Δ133p53α as a regulatory mechanism for p53-mediated senescence
Δ133p53α, a p53 isoform that can inhibit full-length p53, is downregulated at replicative senescence in a manner independent of mRNA regulation and proteasome-mediated degradation. Here we demonstrate that, un...
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Article
Positive feedback between p53 and TRF2 during telomere-damage signalling and cellular senescence
Uncapped telomeres activate a p53-mediated DNA damage response to elicit cellular senescence. In turn, p53 negatively modulates telomere cap** by promoting ubiquitin-mediated degradation of the TRF2 shelteri...
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Article
p53 isoforms Δ133p53 and p53β are endogenous regulators of replicative cellular senescence
p53-mediated replicative cellular senescence is a barrier to tumorigenesis. The p53 isoforms p53β and Δ133p53 are respectively induced and downregulated during replicative senescence. Elevated p53β and reduced...
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Article
Open AccessBoth telomeric and non-telomeric DNA damage are determinants of mammalian cellular senescence
Cellular senescence is a state reached by normal mammalian cells after a finite number of cell divisions and is characterized by morphological and physiological changes including terminal cell-cycle arrest. Th...
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Article
Regulation of hTERT transcription: a target of cellular and viral mechanisms for immortalization and carcinogenesis
A hallmark of human cancer cells is immortal cell growth, which is associated with telomere maintenance by telomerase. The transcriptional regulation of the human telomerase reverse transcriptase (hTERT) gene ...
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Article
Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks
Humans and animals undergo ageing, and although their primary cells undergo cellular senescence in culture, the relationship between these two processes is unclear1,2. Here we show that γ-H2AX foci (γ-foci), whic...
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Article
Identification of a ≦600-kb region on human chromosome 1q42.3 inducing cellular senescence
The introduction of a human chromosome 1 via microcell-mediated chromosome transfer (MMCT) induces the cellular senescence in mouse melanoma B16-F10 cells. The senescent cells maintained still the telomerase a...
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Article
Tumor-specific activation of hTERT-derived promoters by tumor suppressive E1A-mutants involves recruitment of p300/CBP/HAT and suppression of HDAC-1 and defines a combined tumor targeting and suppression system
Adenovirus (Ad) E1A proteins are transcriptional regulators with antioncogenic but also transforming properties. We have previously shown that transformation-defective Ad5 E1A-derivatives are excellent tumor s...
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Article
The human telomerase gene: complete genomic sequence and analysis of tandem repeat polymorphisms in intronic regions
In this work, the full-length hTERT gene was isolated and the sequence of the previously unknown region in intron 6 as well as that of upstream and downstream hTERT regions was determined. We have shown that intr...
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Article
Functional evidence for a telomerase repressor gene on human chromosome 10p15.1
Based on the sites of frequent allelic loss in hepatocellular carcinoma, five normal human chromosomes (2, 4, 5, 10 and 16) were transferred individually into a telomerase-positive human hepatocellular carcino...
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Radio Channel Control for A Multi-Carrier TDMA Microcell System
This paper discusses a radio control channel architecture for a microcellular system which has a radio interface which provides transmission bit rate of less than 500 kb/s, short TDMA frame length of multi-car...
