An alternatively spliced transcript of the PHD3 gene retains prolyl hydroxylase activity

• Published in: Cancer letters Vol. 233; no. 1; pp. 131 - 138
• Main Authors: Cervera, Ana M., Apostolova, Nadezda, Luna-Crespo, Francisco, Sanjuan-Pla, Alejandra, Garcia-Bou, Remedios, McCreath, Kenneth J.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 20-02-2006; Elsevier Limited
• Subjects: Alternative Splicing; Amino Acid Sequence; Base Sequence; Cell Line, Tumor; Cloning; Dioxygenases; Enzymes; Humans; Hydroxylation; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - physiology; Hypoxia-inducible factor-1; Hypoxia-Inducible Factor-Proline Dioxygenases; Molecular Sequence Data; PHD3; Plasmids; Procollagen-Proline Dioxygenase - chemistry; Procollagen-Proline Dioxygenase - genetics; Procollagen-Proline Dioxygenase - metabolism; Prolyl hydroxylase; Proteins; United Kingdom > UK; Alternative splicing; PHD3; Prolyl hydroxylase; Hypoxia-inducible factor-1
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2005.03.004

Cellular response to limiting oxygen levels is managed, in part, by the transcription factor hypoxia-inducible factor 1 (HIF-1), and the prolyl hydroxylase (PHD) family of oxygen-requiring enzymes. In the process of analyzing the expression of
PHD3, we observed the presence of two alternatively processed
PHD3 transcripts, designated
PHD3Δ1 and
PHD3Δ4 . The expression of both
PHD3 and
PHD3Δ1 was observed in all tissues and cell lines tested, although the expression of the novel
PHD3Δ4 appeared to be restricted to primary cancer tissues. The function of
PHD3Δ4 was assessed in transfection experiments showing a preserved prolyl hydroxylase activity. We would submit that
PHD3 variants generated by alternative splicing may be intrinsically involved in the complex system of oxygen sensing.