Alternative splicing of Bcl-2-related genes: functional consequences and potential therapeutic applications


Akgul C., Moulding D. A., Edwards S. W.

CELLULAR AND MOLECULAR LIFE SCIENCES, cilt.61, sa.17, ss.2189-2199, 2004 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 61 Sayı: 17
  • Basım Tarihi: 2004
  • Doi Numarası: 10.1007/s00018-004-4001-7
  • Dergi Adı: CELLULAR AND MOLECULAR LIFE SCIENCES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.2189-2199
  • Anahtar Kelimeler: apoptosis, Bcl-2 family, alternative splicing, antisense
  • Çanakkale Onsekiz Mart Üniversitesi Adresli: Evet

Özet

Apoptosis is a morphologically distinct form of cell death. It is executed and regulated by several groups of proteins. Bcl-2 family proteins are the main regulators of the apoptotic process acting either to inhibit or promote it. More than 20 members of the family have been identified so far and most have two or more isoforms. Alternative splicing is one of the major mechanisms providing proteomic complexity and functional diversification of the Bcl-2 family proteins. Pro- and antiapoptotic Bcl-2 family members should function in harmony for the regulation of the apoptosis machinery, and their relative levels are critical for cell fate. Any mechanism breaking down this harmony by changing the relative levels of these antagonistic proteins could contribute to many diseases, including cancer and neurodegenerative disorders. Recent studies have shown that manipulation of the alternative splicing mechanisms could provide an opportunity to restore the proper balance of these regulator proteins. This review summarises current knowledge on the alternative splicing products of Bcl-2-related genes and modulation of splicing mechanisms as a potential therapeutic approach.