Increased expression of the acid sphingomyelinase-like protein ASML3a in bladder tumors.
OBJECTIVE
The function of the tumor suppressor gene DBCCR1 (deleted in bladder cancer chromosome region 1) is unknown despite data supporting an important role for DBCCR1 in bladder tumorigenesis. DBCCR1 has not yet been placed in a protein family or functional pathway. Protein-protein interactions are crucial for almost every aspect of cellular function. We hypothesized that the discovery of DBCCR1 protein binding partners would yield important clues for solving the mystery of DBCCR1 function.


METHODS
We used the yeast 2-hybrid system to screen an adult human bladder cDNA library for DBCCR1 interacting proteins.


RESULTS
In the screen ASML3a (acid sphingomyelinase-like phosphodiesterase 3a) was identified as a novel DBCCR1 binding partner. Transient transfection of bladder tumor cell lines showed that DBCCR1 over expression in human bladder tumor cells results in the up-regulation of ASML3a RNA and protein expression. ASML3a protein was also differentially expressed in 8 of 12 bladder tumors relative to corresponding normal urothelial tissue.


CONCLUSIONS
It appears that DBCCR1 and ASML3a are involved in the process of bladder tumorigenesis. Their interaction may provide clues to discern their functions.
Wright
Kate O
KO
Department of Pathology, University of Rochester, New York, USA.
Messing
Edward M
EM
Reeder
Jay E
JE
D016475:3T3 Cells; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D005260:Female; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D020539:Sequence Analysis, Protein; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism*
C112308:BRINP1 protein, human; D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C469297:SMPDL3A protein, human; D013108:Sphingomyelin Phosphodiesterase