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Expression and function of bcl-2 proteins in melanoma.

Eberle J, Hossini AM - Curr. Genomics (2008)

Bottom Line: Bcl-2 proteins are critical regulators of mitochondrial membrane permeability and the proapoptotic mitochondrial pathway.The family encloses pro- and antiapoptotic factors encoded by over 15 genes, which frequently give rise to alternative splice products.Antiapoptotic, proapoptotic multidomain, and proapoptotic BH3-only proteins are characterized by the presence of at least one of four Bcl-2 homology domains (BH 1-4).

View Article: PubMed Central - PubMed

Affiliation: Charité - Universitätsmedizin Berlin, Department of Dermatology and Allergy, Skin Cancer Center Charité, Berlin, Germany.

ABSTRACT
Bcl-2 proteins are critical regulators of mitochondrial membrane permeability and the proapoptotic mitochondrial pathway. The family encloses pro- and antiapoptotic factors encoded by over 15 genes, which frequently give rise to alternative splice products. Antiapoptotic, proapoptotic multidomain, and proapoptotic BH3-only proteins are characterized by the presence of at least one of four Bcl-2 homology domains (BH 1-4). Their expression and activities are controlled by survival pathways as MAP kinases and protein kinase B/Akt, which are in touch with a number of transcription factors. In melanoma, the mitochondrial apoptosis pathways and Bcl-2 proteins appear of particular importance for apoptosis resistance, which has been addressed in clinical trials applying antisense-Bcl-2. Overexpression or induction of proapoptotic Bcl-2 proteins as well as the use of small molecule mimetics for the proapoptotic BH3 domain are further promising strategies.

No MeSH data available.


Related in: MedlinePlus

Abbreviations: Cyt C, cytochrome C; IAPs, inhibitors of apoptosis proteins; tBid, truncated Bid; BH3-only, BH3-only proteins; AIF, apoptosis-inducing factor; EndoG, endonuclease G; Apaf-1, apoptosis-activating factor.
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Figure 1: Abbreviations: Cyt C, cytochrome C; IAPs, inhibitors of apoptosis proteins; tBid, truncated Bid; BH3-only, BH3-only proteins; AIF, apoptosis-inducing factor; EndoG, endonuclease G; Apaf-1, apoptosis-activating factor.

Mentions: Different types of cellular damage as well as cellular dysregulation such as oncogene activation induce cell-intrinsic proapoptotic pathways. Highly active is the mitochondrial pathway characterized by a release of mitochondrial proapoptotic factors into the cytoplasm [9]. This step is critically controlled by the family of Bcl-2 proteins (Fig. 1).


Expression and function of bcl-2 proteins in melanoma.

Eberle J, Hossini AM - Curr. Genomics (2008)

Abbreviations: Cyt C, cytochrome C; IAPs, inhibitors of apoptosis proteins; tBid, truncated Bid; BH3-only, BH3-only proteins; AIF, apoptosis-inducing factor; EndoG, endonuclease G; Apaf-1, apoptosis-activating factor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2691663&req=5

Figure 1: Abbreviations: Cyt C, cytochrome C; IAPs, inhibitors of apoptosis proteins; tBid, truncated Bid; BH3-only, BH3-only proteins; AIF, apoptosis-inducing factor; EndoG, endonuclease G; Apaf-1, apoptosis-activating factor.
Mentions: Different types of cellular damage as well as cellular dysregulation such as oncogene activation induce cell-intrinsic proapoptotic pathways. Highly active is the mitochondrial pathway characterized by a release of mitochondrial proapoptotic factors into the cytoplasm [9]. This step is critically controlled by the family of Bcl-2 proteins (Fig. 1).

Bottom Line: Bcl-2 proteins are critical regulators of mitochondrial membrane permeability and the proapoptotic mitochondrial pathway.The family encloses pro- and antiapoptotic factors encoded by over 15 genes, which frequently give rise to alternative splice products.Antiapoptotic, proapoptotic multidomain, and proapoptotic BH3-only proteins are characterized by the presence of at least one of four Bcl-2 homology domains (BH 1-4).

View Article: PubMed Central - PubMed

Affiliation: Charité - Universitätsmedizin Berlin, Department of Dermatology and Allergy, Skin Cancer Center Charité, Berlin, Germany.

ABSTRACT
Bcl-2 proteins are critical regulators of mitochondrial membrane permeability and the proapoptotic mitochondrial pathway. The family encloses pro- and antiapoptotic factors encoded by over 15 genes, which frequently give rise to alternative splice products. Antiapoptotic, proapoptotic multidomain, and proapoptotic BH3-only proteins are characterized by the presence of at least one of four Bcl-2 homology domains (BH 1-4). Their expression and activities are controlled by survival pathways as MAP kinases and protein kinase B/Akt, which are in touch with a number of transcription factors. In melanoma, the mitochondrial apoptosis pathways and Bcl-2 proteins appear of particular importance for apoptosis resistance, which has been addressed in clinical trials applying antisense-Bcl-2. Overexpression or induction of proapoptotic Bcl-2 proteins as well as the use of small molecule mimetics for the proapoptotic BH3 domain are further promising strategies.

No MeSH data available.


Related in: MedlinePlus