Transcription variants of the prostate-specific PrLZ gene and their interaction with 14-3-3 proteins.
We have reported isolation and characterization of the prostate-specific and androgen-regulated PrLZ gene abnormally expressed in prostate cancer. PrLZ is a potential biomarker for prostate cancer and a candidate oncogene promoting cell proliferation and survival in prostate cancer cells. A full delineation of the PrLZ gene and its gene products may provide clues to the mechanisms regulating its expression and function. In this report, we identified three additional exons in the PrLZ gene and recognized five transcript variants from alternative splicing that could be detected by RT-PCR and Western blotting. Structural comparison demonstrated that the PrLZ proteins are highly conserved among species. PrLZ contains multiple potential sites for interaction with other proteins. We used mammalian two-hybrid assays to demonstrate that PrLZ isoforms interact with 14-3-3 proteins, and multiple sites in the PrLZ may be involved in the interaction. Alternative splicing may contribute to abnormally enhanced PrLZ levels in prostate cancer, and interaction with 14-3-3 proteins may be a mechanism by which PrLZ promotes cell proliferation and survival during prostate cancer development and progression. This information is a valuable addition to the investigation of the oncogenic properties of the PrLZ gene.
Wang
Ruoxiang
R
Department of Urology, Emory University School of Medicine, Atlanta, GA 30322, USA. rwang2@emory.edu
He
Hui
H
Sun
Xiaojuan
X
Xu
Jianchun
J
Marshall
Fray F
FF
Zhau
Haiyen
H
Chung
Leland W K
LW
Fu
Haian
H
He
Dalin
D
D048948:14-3-3 Proteins / Q000378:metabolism*; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D017124:Conserved Sequence; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D048948:14-3-3 Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; C114751:TPD52 protein, human