Regulation of Bcl-xL: a little bit of this and a little bit ... : Current Opinion in Oncology (original) (raw)
Therapeutic modalities
Sylvester Comprehensive Cancer Center, Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida, USA
Correspondence to Lawrence H. Boise, Department of Microbiology and Immunology, RMSB Rm 3045A, 1600 NW 10th Ave, Miami, FL 33136, USA; e-mail: [email protected]
Abstract
The Bcl-2 family of proteins are key regulators of apoptosis. Bcl-xL is an anti-apoptotic protein with a high degree of homology to Bcl-2; however, the signals that regulate Bcl-xL and Bcl-2 appear to be different. Levels of Bcl-xL, but not Bcl-2, are increased in response to various survival signals. Furthermore, an inverse correlation between the levels of Bcl-2 and Bcl-xL has been reported for a number of cancers. Although the precise molecules that control Bcl-xL activity are unclear, the STAT, Rel/NF-κB, and Ets transcription factor families have recently been reported to directly regulate the bcl-x gene. Activated Ras, integrin, vitronectin, and hepatocyte growth factor signaling cascades have also been linked to changes in Bcl-xL expression. Bcl-xL can also be affected by post-translational mechanisms. Here we review recent advances in identifying the signaling pathways and factors involved in regulation of the bcl-x gene.
© 2000 Lippincott Williams & Wilkins, Inc.