Regulation of Bcl-xL: a little bit of this and a little bit of STAT.
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-kappaB, 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.
Grad
J M
JM
Sylvester Comprehensive Cancer Center, Department of Microbiology and Immunology, University of Miami School of Medicine, Florida, USA.
Zeng
X R
XR
Boise
L H
LH
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008894:Milk Proteins; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050783:Proto-Oncogene Proteins c-ets; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D051020:bcl-X Protein