Regulation of Sphingosine Kinase in Prostate Cancer Cells
Abstract
Sphingosine kinase 1 (SphK1) and its product sphingosine 1-phosphate (S1P) have been shown to promote cell growth and inhibit apoptosis of tumor cells (reviewed in (1)). Moreover, sphingosine kinase has been shown to be responsible for radioresistance -of certain prostate cancer cells (2). In an effort to understand the regulation of SphK1, we undertook a two-hybrid screen for SphK1-interacting proteins. We found eleven potential interactors. Over the course of the report period, we have focused our efforts on one of these interactors, aminoacylase 1 (Acyl) . Acyl is a metalloprotein that removes amide- linked acyl groups from amino acids, and may play a role in regulating oxidative damage. We have shown that both the C-terminal fragment and full length Acyl co-immunoprecipitate with SphK1. Both proteins also cause a redistribution of SphK1 as observed by immunocytochemistry. Though both 0-terminal and full length proteins reduce SphK1 activity measured in vitro, the C-terminal fragment inhibits while the full length potentiates the effects of SphK1 on proliferation and apoptosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2003
- Accession Number
- ADA420163
Entities
People
- Michael W. Maceyka
Organizations
- Virginia Commonwealth University