Differential alternative splicing of human transglutaminase 4 in benign prostate hyperplasia and prostate cancer.
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.
Cho
Sung-Yup
SY
Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center (AARC), Seoul National University College of Medicine, Seoul 110-799, Korea.
Choi
Kyungho
K
Jeon
Ju-Hong
JH
Kim
Chai-Wan
CW
Shin
Dong-Myung
DM
Lee
Jong Bouk
JB
Lee
Sang Eun
SE
Kim
Choung-Soo
CS
Park
Jeong-Soo
JS
Jeong
Eui Man
EM
Jang
Gi-Yong
GY
Song
Kye-Yong
KY
Kim
In-Gyu
IG
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
D007527:Isoenzymes; C418702:transglutaminase 4; D011503:Transglutaminases