title: Differential alternative splicing of human transglutaminase 4 in benign prostate hyperplasia and prostate cancer.
abstract: Transglutaminase 4 is a member of enzyme family that catalyzes calcium-dependent posttranslational modification of proteins. Although transglutaminase 4 has been shown to have prostate-restricted expression pattern, little is known about the biological function of transglutaminase 4 in human. To gain insight into its role in prostate, we analyzed the expression status of human transglutaminase 4 in benign prostate hyperplasia (BPH) and prostate cancer (PCa). Unexpectedly, RT-PCR and nucleotide sequence analysis showed four alternative splicing variants of transglutaminase 4: transglutaminase 4-L, -M (-M1 and -M2) and -S. The difference between transglutaminase 4-M1 and -M2 is attributed to splicing sites, but not nucleotide size. The deduced amino acid sequences showed that transglutaminase 4-L, -M1 and -M2 have correct open reading frames, whereas transglutaminase 4-S has a truncated reading frame. RT-PCR analysis of clinical samples revealed that transglutaminase 4-M and -S were detected in all tested prostate tissue (80 BPH and 48 PCa). Interestingly, transglutaminase 4-L was found in 56% of BPH (45 out of 80) and only in 15% of PCa (7 out of 48). However, transglutaminase 4-L expression did not correlate with serum prostate-specific antigen (PSA) level, prostate volumes or PSA densities. These results will provide a clue to future investigation aiming at delineating physiological and pathological roles of human transglutaminase 4.
authors.affiliation: Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center (AARC), Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Sung-Yup
authors.initials: SY
authors.lastname: Cho
authors.forename: Kyungho
authors.initials: K
authors.lastname: Choi
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
authors.forename: Chai-Wan
authors.initials: CW
authors.lastname: Kim
authors.forename: Dong-Myung
authors.initials: DM
authors.lastname: Shin
authors.forename: Jong Bouk
authors.initials: JB
authors.lastname: Lee
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Choung-Soo
authors.initials: CS
authors.lastname: Kim
authors.forename: Jeong-Soo
authors.initials: JS
authors.lastname: Park
authors.forename: Eui Man
authors.initials: EM
authors.lastname: Jeong
authors.forename: Gi-Yong
authors.initials: GY
authors.lastname: Jang
authors.forename: Kye-Yong
authors.initials: KY
authors.lastname: Song
authors.forename: In-Gyu
authors.initials: IG
authors.lastname: Kim
mesh_terms: D000368:Aged; D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D011470:Prostatic Hyperplasia / Q000201:enzymology* / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics*; D012441:Saccharomyces cerevisiae; D011503:Transglutaminases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D007527:Isoenzymes; C418702:transglutaminase 4; D011503:Transglutaminases