Abstract：
:Splice variants of certain genes impact on genetic biodiversity in mammals. The tumor suppressor TP53 gene (encoding p53) plays an important role in the regulation of tumorigenesis in hepatocellular carcinoma (HCC). Δ40p53α is a naturally occurring p53 isoform that lacks the N-terminal transactivation domain, yet little is known about the role of Δ40p53α in the development of HCC. Here, we first report on the role of Δ40p53α in HCC cell lines. In the TP53+/Δ40 cell clones, clonogenic activity and cell survival dramatically decreased, whereas the percentage of senescence-associated β-galactosidase (SA-β-gal)-positive cells and p21 (also known as WAF1, CIP1 and CDKN1A) expression significantly increased. These observations were clearly attenuated in the TP53+/Δ40 cell clones after Δ40p53α knockdown. In addition, exogenous Δ40p53 expression significantly suppressed cell growth in HCC cells with wild-type TP53, and in those that were mutant or null for TP53 Notably, Δ40p53α-induced tumor suppressor activity was markedly attenuated in cells expressing the hot-spot mutant Δ40p53α-R175H, which lacks the transcription factor activity of p53. Moreover, Δ40p53α expression was associated with increased full-length p53 protein expression. These findings enhance the understanding of the molecular pathogenesis of HCC and show that Δ40p53α acts as an important tumor suppressor in HCC cells.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Ota A,Nakao H,Sawada Y,Karnan S,Wahiduzzaman M,Inoue T,Kobayashi Y,Yamamoto T,Ishii N,Ohashi T,Nakade Y,Sato K,Itoh K,Konishi H,Hosokawa Y,Yoneda Mdoi
10.1242/jcs.190736subject
Has Abstractpub_date
2017-02-01 00:00:00pages
614-625issue
3eissn
0021-9533issn
1477-9137pii
jcs.190736journal_volume
130pub_type
杂志文章abstract：:Focal adhesions are complex multi-molecular structures that link the actin cytoskeleton to the extracellular matrix through integrin adhesion receptors and play a key role in regulation of many cellular functions. LAR (also known as PTPRF) is a receptor protein tyrosine phosphatase that regulates PDGF signalling and l...
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doi：
更新日期：1978-10-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1976-08-01 00:00:00
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journal_title：Journal of cell science
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更新日期：2005-06-15 00:00:00
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pub_type： 杂志文章
doi：10.1242/jcs.00523
更新日期：2003-07-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-05-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1977-04-01 00:00:00
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doi：
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doi：
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doi：
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journal_title：Journal of cell science
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更新日期：1996-08-01 00:00:00
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