TBC1D3, a hominoid oncoprotein, is encoded by a cluster of paralogues located on chromosome 17q12.
TBC1D3 is a member of the TBC1 domain family of proteins that stimulates the intrinsic GTPase activity of RAB5A, an essential actor in early endosome trafficking. Oncogenic properties of TBC1D3 have been demonstrated previously both in vitro and in mouse models. Although the oncogenic mechanism of TBC1D3 has yet to be elucidated, the TBC1D3 locus (chromosome 17q12) is amplified in 15% of primary prostate tumors. Here, we describe eight highly related TBC1D3 paralogues located within that genomic region, potentially encoding six variant TBC1D3 proteins. We found that human tissues display specific transcription patterns of these paralogues. Furthermore, that pattern was altered in several primary prostate tumors in comparison to healthy prostate tissues. Potential TBC1D3 oncogenic mechanisms are discussed in light of these results.
Hodzic
Didier
D
Department of Cell Biology and Physiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Kong
Chen
C
Department of Cell Biology and Physiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Wainszelbaum
Marisa J
MJ
Department of Cell Biology and Physiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Charron
Audra J
AJ
Department of Cell Biology and Physiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Su
Xiong
X
Department of Cell Biology and Physiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Stahl
Philip D
PD
Department of Cell Biology and Physiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA. Electronic address: pstahl@cellbiology.wustl.edu.
D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism; D018628:Gene Dosage; D014644:Genetic Variation; D006801:Humans; D008297:Male; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes / Q000235:genetics*; D009928:Organ Specificity; D010920:Placenta / Q000378:metabolism; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D020690:GTPase-Activating Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C467563:TBC1D3 protein, human