Over-expression of Bim α3, a novel isoform of human Bim, result in cell apoptosis

Chen, Jin Zhong; Ji, Chao; Gu, Siyi; Li, Ji Xi; Zhao, En Peng; Huang, Yan; Huang, Lu; Kong, Ying; Xie, Yi; Mao, Yu

doi:10.1016/j.biocel.2003.12.015

Cited by 11 publications

(13 citation statements)

References 17 publications

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“…Up to date, at least 16 Bim isoforms have been identified which differentially expressed in various kinds of tissues [16][17][18][19]. It is expected that the number will expand as more and more new exons and novel assembling manners are observed.…”

Section: Discussionmentioning

confidence: 99%

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Identification and characterization of BH3 domain protein Bim and its isoforms in human hepatocellular carcinomas

et al. 2007

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BH3-only protein Bim is a critical regulator of apoptosis and plays an essential role in mammalian development, but the characterization of Bim and its isoforms in hepatocellular carcinoma (HCC) has not been studied before. Here we investigated the expression, distribution, regulation and role of Bim isoforms in HCC cells. Fifteen Bim isoforms were identified in HCC, with six newly identified isoforms and two newly identified exons. Among of them, Bim EL, L, S, a1, a2, a3, b2, b4 and b6 are abundant isoforms according to their mRNA levels. However only Bim EL, L and S proteins could be clearly detected. Bim mRNA and protein were strongly expressed in HCC tissues compared to relevant non-tumorous regions, but the ratio of variant isoforms showed no difference between tumorous and non-tumorous tissues. Bim isoforms were differentially regulated after chemotherapeutic drug 5-Fluorouracil (5-FU) treatment. Interestingly, Bim EL, L and S, the isoforms known to induce apoptosis strongly, are the least inducible isoforms at their mRNA levels when exposed to the stress, suggesting that post-transcriptional rather than transcriptional, modulations may play a role to enhance their functions. Finally, overexpression of Bim EL, L, S and all alpha isoforms induced apoptosis in HCC cells, while overexpression of Bim beta isoforms showed no effects on cell survival after 5-FU treatment. In conclusion, Bim alpha isoforms appears to have a role in the regulation of apoptosis in HCC cells, which may contribute to not only the growth of tumor cells but also the sensitivity of HCC cells to chemotherapy.

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Section: Discussionmentioning

confidence: 99%

“…Bim S (96 residues) is the most potent inducer of apoptosis among the Bim isoforms. Recently, alternatively splicing products of Bim have been identified [16][17][18][19]. Bim isoforms have been classified to two major groups--alpha and beta, according to their apoptotic-inducing characteristics [19].…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of BH3 domain protein Bim and its isoforms in human hepatocellular carcinomas

et al. 2007

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“…Z. Chen et al, 2004), novel regulators of NF-kappaB pathways (H. Gao et al, 2004), heterotic effects at the single-locus level (Hua et al, 2003), and bHLH-Zip gene role in human spermatogenesis (Sha et al, 2003).…”

Section: Resultsmentioning

confidence: 99%

The Emergence of Modern Biotechnology in China

Lakhan¹

2006

InSITE Conference

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“…A lot of studies are focused on activation of BHD proteins (BAX, BAK). Letai et al,16 found that short peptides representing the α-helical BH3 domains of BID or BIM are capable of inducing oligomerization of BAK and BAX releasing cytochrome c. BIM peptide is the BH3 domain of this protein that binds with BAX protein and it has been demonstrated 6,22,23 that the sequence between residues 146-166 are sufficient to interact with BAX and activate apoptosis. Recent studies 24 revealed that BH3 domain peptides (BIM or BID) with enhanced α-helical structures bound with greater affinity to BAX, activating cell death.…”

Section: New Therapies In Cancer Based On the Inhibition Of Pro-survimentioning

confidence: 99%

Apoptosis’ activation associated to BH3 only domain and BCL-2 homology domain proteins: new way to design anti-cancer drugs

Delgado¹,

Torres²,

Milián³

2019

JCPCR

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Cancer is one of the leading health problems we face today. A possible way to develop specific treatments is through the identification and understanding of proteins responsible for the regulation of apoptosis. Apoptosis is a cell suicide that is critically important for organ development and tissue turnover.1 The BCL-2 homology domain (BHD) and BH3-only domain (BOD) are pro-apoptotic proteins that mediate mitochondrial damage, inducing intrinsic pathway cell death. This review wants to explain how BOD and BHD proteins trigger mitochondrial events associated to apoptosis to develop treatments that can promote apoptosis in cancer cells.

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Over-expression of Bim α3, a novel isoform of human Bim, result in cell apoptosis

Cited by 11 publications

References 17 publications

Identification and characterization of BH3 domain protein Bim and its isoforms in human hepatocellular carcinomas

Identification and characterization of BH3 domain protein Bim and its isoforms in human hepatocellular carcinomas

The Emergence of Modern Biotechnology in China

Apoptosis’ activation associated to BH3 only domain and BCL-2 homology domain proteins: new way to design anti-cancer drugs

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