DBC2 significantly influences cell-cycle, apoptosis, cytoskeleton and membrane-trafficking pathways.
The tumor suppressor DBC2 belongs to a previously uncharacterized gene family, RHOBTB (Bric-a-brac, Tramtrack, Broad-complex). The biological roles of RHOBTB proteins, including DBC2, remain unclear. To understand the physiological functions of DBC2, a global approach was applied. Expression of DBC2 was manipulated in HeLa cells and RNA profiling of the cells was performed by microarray analyses. DBC2 was introduced into HeLa cells by a mammalian expression vector with a constitutive promoter. DBC2 knockdown was achieved by RNA interference with small interfering RNA. RNA profiles of these samples were performed by microarray analysis using Affymetrix GeneChip HG-U133A 2.0. The microarray data were analyzed by Microarray Suite 5.0 (MAS 5.0) and Robust Multichip Average (RMA). A list of genes whose expression was significantly altered (p<0.001) was generated and overlaid onto a cellular pathway map in the Ingenuity Systems' Pathway Knowledge Base (Winter'04 Release). Two networks were found to react substantially to DBC2 expression; namely, more than half of participating genes are affected. One of the networks regulates cell growth through cell-cycle control and apoptosis. The other network is related to cytoskeleton and membrane trafficking. Our findings suggest that the biological roles of DBC2 are related directly and/or indirectly to these cellular machineries.
Siripurapu
Veeraiah
V
Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Meth
Jennifer
J
Kobayashi
Noriko
N
Hamaguchi
Masaaki
M
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002462:Cell Membrane / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D021381:Protein Transport; D034622:RNA Interference; D012260:Ribonucleases / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C497336:RHOBTB2 protein, human; D025521:Tumor Suppressor Proteins; C118970:USH1C protein, human; D012260:Ribonucleases; D019204:GTP-Binding Proteins