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Human Delta1-pyrroline-5-carboxylate synthase: function and regulation
C-A A Hu1, S Khalil, S Zhaorigetu
1Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA. AHu@salud.unm.edu
Amino Acids
|April 11, 2008
Summary
Mammalian Delta(1)-pyrroline-5-carboxylate synthase (P5CS) has two isoforms. P5CS.long is widely expressed and hormone-regulated, while P5CS.short is gut-specific and inhibited by ornithine. P5CS.long is upregulated by p53 in colorectal cancer cells.
Area of Science:
- Biochemistry
- Molecular Biology
- Enzymology
Background:
- Mammalian Delta(1)-pyrroline-5-carboxylate synthase (P5CS) is a key mitochondrial enzyme in amino acid biosynthesis.
- Two P5CS protein isoforms, P5CS.short and P5CS.long, arise from alternative splicing.
- P5CS.short is gut-specific and ornithine-inhibited, while P5CS.long is ubiquitous and hormone-responsive.
Purpose of the Study:
- To characterize the two P5CS isoforms and their regulation.
- To investigate the role of P5CS.long in p53-mediated apoptosis.
- To explore hormonal and alternative splicing regulation of P5CS.
Main Methods:
- Quantitative proteomics to assess P5CS.long expression.
- Functional genomic analysis to identify p53-binding sites.
- Analysis of P5CS expression in human cell lines and response to hormones.
Main Results:
- Human cell lines predominantly express P5CS.long, not P5CS.short.
- P5CS.long expression is modulated by hormones like hydrocortisone, dexamethasone, and estradiol.
- P5CS.long is upregulated by p53 in DLD-1 colorectal cancer cells, with identified p53-binding sites in the P5CS gene.
- Overexpression of either P5CS isoform did not affect cell growth or survival.
Conclusions:
- P5CS.long is a p53 downstream effector in colorectal cancer cells.
- Hormonal and alternative splicing mechanisms regulate P5CS.short expression.
- Further research is needed to elucidate the precise roles of P5CS isoforms and their regulation.
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