Tob2, a novel anti-proliferative Tob/BTG1 family member, associates with a component of the CCR4 transcriptional regulatory complex capable of binding cyclin-dependent kinases.
Human cDNAs encoding a novel member of Tob/BTG1 anti-proliferative family proteins were cloned. The putative protein product termed Tob2 consisted of 344 amino acids with high similarity to the Tob protein. The tob2 mRNA was 4.1 kb long and was ubiquitously expressed in human adult tissues, as was revealed by Northern blot hybridization. However, further in situ hybridization analysis showed a characteristic expression of the tob2 mRNA in oocytes, suggesting a unique role of Tob2 in oogenesis. Like the Tob protein, Tob2 inhibited cell cycle progression from the G0/G1 to S phases. Intriguingly, the amino-terminal half of Tob2 as well as that of Tob was associated with a human homologue of yeast Caf1, a component of the CCR4 transcription factor complex. Moreover, Caf1 was associated with cyclin dependent kinases. These data suggested that both Tob and Tob2 were involved in cell cycle regulation through their interaction with Caf1. Finally, the tob2 gene was mapped to human chromosome 22q13.1-q13.31.
Ikematsu
N
N
Department of Oncology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Yoshida
Y
Y
Kawamura-Tsuzuku
J
J
Ohsugi
M
M
Onda
M
M
Hirai
M
M
Fujimoto
J
J
Yamamoto
T
T
D016475:3T3 Cells / Q000166:cytology / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D005095:Exoribonucleases; D016193:G1 Phase / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011817:Rabbits; D012097:Repressor Proteins; D012260:Ribonucleases; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
C489552:Btg1 protein, mouse; C489780:CNOT8 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C098669:TOB1 protein, human; C402648:TOB2 protein, human; C490903:Tob1 protein, mouse; C485732:Tob2 protein, mouse; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C074086:BTG1 protein, human; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495900:CDK4 protein, human; C495893:Cdk2 protein, mouse; C495902:Cdk4 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; C489778:Cnot7 protein, mouse; D005095:Exoribonucleases; D012260:Ribonucleases