Current Genomics

Christian Néri
Institute of Biology Paris-Seine
CNRS UMR 8256 and UPMC
Paris, 75005
France

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Expression and Function of Bcl-2 Proteins in Melanoma

Author(s): Jurgen Eberle and Amir M. Hossini

Affiliation: Charite–Universitatsmedizin Berlin, Department of Dermatology and Allergy, Skin Cancer Center Charite, Charite Campus Mitte, Chariteplatz 1, 10117 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.

Keywords: Melanoma, apoptosis, Bcl-2 proteins

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Article Details

VOLUME: 9
ISSUE: 6
Page: [409 - 419]
Pages: 11
DOI: 10.2174/138920208785699571
Price: $58