Tubulin tyrosine ligase like 12 links to prostate cancer through tubulin posttranslational modification and chromosome ploidy.
Prostate cancer is a common cause of death, and an important goal is to establish the pathways and functions of causative genes. We isolated RNAs that are differentially expressed in macrodissected prostate cancer samples. This study focused on 1 identified gene, TTLL12, which was predicted to modify tubulins, an established target for tumor therapy. TTLL12 is the most poorly characterized member of a recently discovered 14-member family of proteins that catalyze posttranslational modification of tubulins. We show that human TTLL12 is expressed in the proliferating layer of benign prostate. Expression increases during cancer progression to metastasis. It is highly expressed in many metastatic prostate cancer cell lines. It partially colocalizes with vimentin intermediate filaments and cellular structures containing tubulin, including midbodies, centrosomes, intercellular bridges and the mitotic spindle. Downregulation of TTLL12 affects several posttranslational modifications of tubulin (detyrosination and subsequent deglutamylation and polyglutamylation). Overexpression alters chromosomal ploidy. These results raise the possibility that TTLL12 could contribute to tumorigenesis through effects on the cytoskeleton, tubulin modification and chromosome number stability. This study contributes a step toward developing more selective agents targeting microtubules, an already successful target for tumor therapy.
Wasylyk
Christine
C
Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR 7104 CNRS UDS-U 964 INSERM, Illkirch, France.
Zambrano
Alberto
A
Zhao
Chunhua
C
Brants
Jan
J
Abecassis
Joseph
J
Schalken
Jack A
JA
Rogatsch
Hermann
H
Schaefer
Georg
G
Pycha
Armin
A
Klocker
Helmut
H
Wasylyk
Bohdan
B
D002453:Cell Cycle / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D043171:Chromosomal Instability; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D010453:Peptide Synthases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011003:Ploidies; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D014404:Tubulin / Q000378:metabolism*
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014404:Tubulin; D010453:Peptide Synthases; C553200:TTLL12 protein, human; C112698:tubulin polyglutamylase