Abstract |
We identified seven putative splice variants of the human IG20 gene. Four variants namely, IG20, MADD, IG20-SV2 and DENN-SV are expressed in human tissues. While DENN-SV is constitutively expressed in all tissues, expression of IG20 appears to be regulated. Interestingly, overexpression of DENN-SV enhanced cell replication and resistance to treatments with TNFalpha, vinblastine, etoposide and gamma-radiation. In contrast, IG20 expression suppressed cell replication and increased susceptibility to the above treatments. Moreover, cells that were resistant and susceptible to TNFalpha-induced apoptosis exclusively expressed endogenous DENN-SV and IG20, respectively. When PA-1 ovarian cancer cells that are devoid of endogenous IG20 variant, but express higher levels of DENN-SV, were transfected with IG20, they showed reduced cell proliferation and increased susceptibility to apoptosis induced by TNFalpha, TRAIL and gamma-radiation. This indicated that overexpression of IG20 can override endogenous DENN-SV function. CrmA reversed the effects of IG20, but not DENN-SV. In contrast, dominant-negative- I-kappa B reversed the effects of DENN-SV, but not IG20, and showed that DENN-SV most likely exerted its effects through NFkappaB activation. Together, our data show that IG20 gene can play a novel and significant role in regulating cell proliferation, survival and death through alternative mRNA splicing.
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Authors | Elena V Efimova, Adeeb M Al-Zoubi, Osvaldo Martinez, Shashi Kaithamana, Shenfeng Lu, Takayasu Arima, Bellur S Prabhakar |
Journal | Oncogene
(Oncogene)
Vol. 23
Issue 5
Pg. 1076-87
(Feb 05 2004)
ISSN: 0950-9232 [Print] England |
PMID | 14716293
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antineoplastic Agents
- Death Domain Receptor Signaling Adaptor Proteins
- Guanine Nucleotide Exchange Factors
- I-kappa B Proteins
- MADD protein, human
- NF-kappa B
- Tumor Necrosis Factor-alpha
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Topics |
- Alternative Splicing
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Cell Division
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Death Domain Receptor Signaling Adaptor Proteins
- Gene Expression Regulation
- Genetic Variation
- Guanine Nucleotide Exchange Factors
(genetics)
- HeLa Cells
- Humans
- I-kappa B Proteins
(genetics, pharmacology)
- NF-kappa B
(metabolism)
- Transfection
- Tumor Necrosis Factor-alpha
(pharmacology)
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