ANA, a novel member of Tob/BTG1 family, is expressed in the ventricular zone of the developing central nervous system

Yoshida, Yutaka; Matsuda, Satoru; Ikematsu, Naoko; Kawamura-Tsuzuku, Junko; Inazawa, Johji; Umemori, Hisashi; Yamamoto, Tadashi

doi:10.1038/sj.onc.1201805

Cited by 105 publications

(107 citation statements)

References 13 publications

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“…This function may be common to other members of the BTG/TOB family. Like BTG2 TIS21/PC3 , BTG3/ANA is expressed in the neuroepithelial cells of the ventricular zone of the developing central nervous system (Yoshida et al, 1998). BTG2 TIS21/PC3 and BTG3/ANA may thus have overlapping roles in the growth arrest of neural precursor cells at the time when the commitment of the precursor cells to the neural or glial lineage occurs.…”

Section: Discussionmentioning

confidence: 99%

“…The human BTG2 TIS21/PC3 gene is a member of a newly identified family of six independent antiproliferative genes, namely, BTG1, ANA/BTG3, PC3B, TOB, TOB2 (Rouault et al, 1992;Matsuda et al, 1996;Guehenneux et al, 1997;Yoshida et al, 1998;Ikematsu et al, 1999;Buanne et al, 2000;Tirone, 2001). Although the biological functions of the BTG2 TIS21/PC3 protein remain to be elucidated, several studies have attempted to identify the different cues capable of inducing its expression.…”

Section: Introductionmentioning

confidence: 99%

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BTG2TIS21/PC3 induces neuronal differentiation and prevents apoptosis of terminally differentiated PC12 cells

et al. 2002

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The p53-transcriptional target, BTG2 TIS21/PC3 , was previously identified as an antiproliferative gene. However, the precise biological functions of the protein product remain to be elucidated. BTG2 TIS21/PC3 expression is induced in vivo during neurogenesis, and the gene is transiently expressed in vitro in rat pheochromocytoma PC12 cells after induction of neuronal differentiation by addition of nerve growth factor (NGF). These observations suggest that BTG2 TIS21/PC3 is functionally significant during the neuronal differentiation process. To test this hypothesis, a vector that expressed BTG2 TIS21/PC3 under the control of an inducible promoter was introduced into PC12 cells. Growth arrest and differentiation in response to NGF were greatly enhanced by BTG2 TIS21/PC3 overexpression. Furthermore, an antisense oligonucleotide complementary to BTG2 TIS21/PC3 mRNA, which was able to inhibit endogenous BTG2 TIS21/PC3 expression, triggered programmed cell death in differentiated PC12 cells. These observations confirm that BTG2 TIS21/PC3 expression promotes neuronal differentiation and that it is required for survival of terminally differentiated cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

BTG2TIS21/PC3 induces neuronal differentiation and prevents apoptosis of terminally differentiated PC12 cells

et al. 2002

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“…1,[2][3][4][5][6][7] Conversely, the antiproliferative activity of TOB is impaired in the presence of exogenously coexpressed Cyclin D1. 7 TOB's antiproliferative activity is regulated through phosphorylation and nuclear localization.…”

Section: Uiccmentioning

confidence: 99%

TOB suppresses breast cancer tumorigenesis

O’Malley

Zhang

et al. 2009

Intl Journal of Cancer

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Transducer of ErbB-2 (TOB) is a member of the TOB/Btg gene family. A role for TOB in the suppression of human tumorigenesis has been proposed, based on the observations that TOB-knockout mice spontaneously form tumors and TOB expression is lost in human lung and thyroid cancers. However, the role of TOB in human breast cancer remains unknown. To evaluate the this role, we screened a panel of breast cancer cell lines for TOB expression levels and found that they are inversely correlated with the tumorigenicity and metastatic potential of the cell lines. In addition, we demonstrated for the first time that TOB expression is inversely correlated with breast cancer progression in clinical specimens. These results strongly indicate that the loss of TOB expression plays a role in breast cancer progression. We have also provided the first evidence that TOB functions as a tumor suppressor in breast cancer MCF-7 cells, using gain-of-function and loss-offunction approaches to manipulate TOB expression. Cell-cycle analysis further revealed that TOB can prolong the G1-S phase transition by inducing arrest at G1-S phase. Moreover, upregulation of the cyclin-dependent kinase inhibitor p27 and downregulation of the antiapoptotic proteins Bcl-2 and Bcl-XL were observed in MCF7/TOB transfectants. Conversely, opposite results were observed in shRNA-TOB transfectants. Furthermore, decreased activity of Erk2, AKT, CrkL, PDK1, and Smads were observed in TOB-overexpressing cells. Taken together, these data provide evidence that TOB can function as a tumor suppressor in breast cancer through modulation and regulation of multiple signaling pathways. ' UICCKey words: TOB; ErbB-2; tumor suppressor Cell growth and differentiation in normal tissues are controlled by a balance of 2 opposing signaling pathways, namely positive and negative signaling. A Transducer of ErbB-2 (TOB), known as TOB/TOB1, is ubiquitously expressed in human adult tissues and was first identified by screening an expression library that detected protein-protein interactions with an ErbB2 probe. 1 The TOB gene is located on chromosome 17q21, telomeric to the BRCA1 locus. TOB is a 45-kDa protein belonging to the TOB/BTG family, which includes proteins, such as PC3/TIS21/BTG2, BTG1, TOB2, ANA, BTG3, PC3K and others. These proteins share a highly conserved amino-terminal region known as the Btg homology domain.Overexpression of TOB/BTG family proteins negatively regulates the cell cycle by inhibiting G1 progression. 1,2-7 Conversely, the antiproliferative activity of TOB is impaired in the presence of exogenously coexpressed Cyclin D1. 7 TOB's antiproliferative activity is regulated through phosphorylation and nuclear localization. In its active state, TOB is unphosphorylated and it is inactivated by phosphorylation. Growth factor stimulation of the RTK/Ras/MAPK pathway results in rapid phosphorylation of these sites by Erk1and Erk2. 8 TOB is also phosphorylated via the Akt pathway by the serine/threonine kinase p90rsk1. 9 In addition, the antiproliferative activity of ...

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“…By contrast, it is lower in differentiated tissues such as muscle or nerve adult tissues (Rouault et al, 1992). Initially, Rouault et al (1992) demonstrated the strong antiproliferative activity of BTG1, more recently established for other members of the BTG family, such as BTG2 (Rouault et al, 1996), Tob (Matsuda et al, 1996) and BTG3 (Yoshida et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Coactivation of nuclear receptors and myogenic factors induces the major BTG1 influence on muscle differentiation

et al. 2005

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The btg1 (B-cell translocation gene 1) gene coding sequence was isolated from a translocation break point in a case of B-cell chronic lymphocytic leukaemia. We have already shown that BTG1, considered as an antiproliferative protein, strongly stimulates myoblast differentiation. However, the mechanisms involved in this influence remained unknown. In cultured myoblasts, we found that BTG1 stimulates the transcriptional activity of nuclear receptors (T3 and all-trans retinoic acid receptors but not RXRa and PPARc), c-Jun and myogenic factors (CMD1, Myf5, myogenin). Immunoprecipitation experiments performed in cells or using in vitro-synthesized proteins and GST pull-down assays established that BTG1 directly interacts with T3 and all-trans retinoic acid receptors and with avian MyoD (CMD1). These interactions are mediated by the transactivation domain of each transcription factor and the A box and C-terminal part of BTG1. NCoR presence induces the ligand dependency of the interaction with nuclear receptors. Lastly, deletion of BTG1 interacting domains abrogates its ability to stimulate nuclear receptors and CMD1 activity, and its myogenic influence. In conclusion, BTG1 is a novel important coactivator involved in the regulation of myoblast differentiation. It not only stimulates the activity of myogenic factors, but also of nuclear receptors already known as positive myogenic regulators.

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ANA, a novel member of Tob/BTG1 family, is expressed in the ventricular zone of the developing central nervous system

Cited by 105 publications

References 13 publications

BTG2TIS21/PC3 induces neuronal differentiation and prevents apoptosis of terminally differentiated PC12 cells

BTG2TIS21/PC3 induces neuronal differentiation and prevents apoptosis of terminally differentiated PC12 cells

TOB suppresses breast cancer tumorigenesis

Coactivation of nuclear receptors and myogenic factors induces the major BTG1 influence on muscle differentiation

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