BTG1

B-cell translocation gene 1, anti-proliferative
Identifiers
Symbol	BTG1
External IDs	OMIM: 109580 MGI: 88215 HomoloGene: 37521 GeneCards: BTG1 Gene
Gene ontology Molecular function • transcription cofactor activity • protein binding • enzyme binding • kinase binding Cellular component • nucleus • cytoplasm Biological process • regulation of transcription, DNA-templated • negative regulation of cell proliferation • cell migration • negative regulation of cell growth • positive regulation of endothelial cell differentiation • positive regulation of myoblast differentiation • positive regulation of angiogenesis • positive regulation of fibroblast apoptotic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	694	12226
Ensembl	ENSG00000133639	ENSMUSG00000036478
UniProt	P62324	P62325
RefSeq (mRNA)	NM_001731	NM_007569
RefSeq (protein)	NP_001722	NP_031595
Location (UCSC)	Chr 12: 92.14 – 92.15 Mb	Chr 10: 96.62 – 96.62 Mb
PubMed search

Protein BTG1 is a protein that in humans is encoded by the BTG1 gene.^[1][2]

Function

The BTG1 gene locus has been shown to be involved in a t(8;12)(q24;q22) chromosomal translocation in a case of B-cell chronic lymphocytic leukemia. It is a member of a family of antiproliferative genes. BTG1 expression is maximal in the G0/G1 phases of the cell cycle and downregulated when cells progressed through G1. It negatively regulates cell proliferation.^[2]

Interactions

BTG1 has been shown to interact with:

• CNOT7,^[3][4]
• CNOT8,^[4][5]
• HOXB9,^[6] and
• PRMT1.^[7][8]

Clinical relevance

Recurrent mutations in this gene have been associated to cases of diffuse large B-cell lymphoma.^[9][10]

Maintenance of adult neural stem cells

Recent data, obtained in a new model of mouse lacking the BTG1 gene, indicate that BTG1 is essential for the proliferation and expansion of stem cells in the adult neurogenic niches, i.e. the dentate gyrus and subventricular zone. In particular, BTG1 keeps adult neural stem cells in quiescence, preserving the neural stem cells pool from depletion; in fact, in absence of BTG1, the stem and progenitor cells initially hyper proliferate and then in the longer period lose the ability to proliferate and expand (;^[11] see for review:^[12]). Other recent data indicate that physical exercise can fully reconstitute the proliferative defect of stem cells that follows the ablation of the BTG1 gene, suggesting that the pool of neural stem cells maintains a hidden form of plasticity which is tightly controlled by BTG1; hence, BTG1 might prevent the depletion of stem cells in the presence of strong neurogenic stimuli or of neural degenerative stimuli.^[13]

Btg1 plays a role also in the expansion of cerebellar granule precursor cells. In fact the deletion of Btg1 leads in mouse to uncontrolled proliferation of the cerebellar precursor cells during the early postnatal period. Consequently, in the adult, the cerebellum lacking Btg1 is significantly larger and the motor coordination is heavily impaired.^[14]

The closest homolog of BTG1 is BTG2, which also controls the proliferation and differentiation of adult neural stem cells; the role of BTG2, however, appears to differ from that of BTG1 being probably more relevant in controlling the terminal differentiation of neural stem and progenitor cells in the adult neurogenic niches.^[12]

References

1. Iwai K, Hirata K, Ishida T, Takeuchi S, Hirase T, Rikitake Y, Kojima Y, Inoue N, Kawashima S, Yokoyama M (March 2004). "An anti-proliferative gene BTG1 regulates angiogenesis in vitro". Biochem Biophys Res Commun 316 (3): 628–35. doi:10.1016/j.bbrc.2004.02.095. PMID 15033446.
2. "Entrez Gene: BTG1 B-cell translocation gene 1, anti-proliferative".
3. Bogdan JA, Adams-Burton C, Pedicord DL, Sukovich DA, Benfield PA, Corjay MH, Stoltenborg JK, Dicker IB (December 1998). "Human carbon catabolite repressor protein (CCR4)-associative factor 1: cloning, expression and characterization of its interaction with the B-cell translocation protein BTG1". Biochem. J. 336 336 (2): 471–81. PMC 1219893. PMID 9820826.
4. Prévôt D, Morel AP, Voeltzel T, Rostan MC, Rimokh R, Magaud JP, Corbo L (March 2001). "Relationships of the antiproliferative proteins BTG1 and BTG2 with CAF1, the human homolog of a component of the yeast CCR4 transcriptional complex: involvement in estrogen receptor alpha signaling pathway". J. Biol. Chem. 276 (13): 9640–8. doi:10.1074/jbc.M008201200. PMID 11136725.
5. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
6. Prévôt D, Voeltzel T, Birot AM, Morel AP, Rostan MC, Magaud JP, Corbo L (January 2000). "The leukemia-associated protein Btg1 and the p53-regulated protein Btg2 interact with the homeoprotein Hoxb9 and enhance its transcriptional activation". J. Biol. Chem. 275 (1): 147–53. doi:10.1074/jbc.275.1.147. PMID 10617598.
7. Lin WJ, Gary JD, Yang MC, Clarke S, Herschman HR (June 1996). "The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase". J. Biol. Chem. 271 (25): 15034–44. doi:10.1074/jbc.271.25.15034. PMID 8663146.
8. Berthet C, Guéhenneux F, Revol V, Samarut C, Lukaszewicz A, Dehay C, Dumontet C, Magaud JP, Rouault JP (January 2002). "Interaction of PRMT1 with BTG/TOB proteins in cell signalling: molecular analysis and functional aspects". Genes Cells 7 (1): 29–39. doi:10.1046/j.1356-9597.2001.00497.x. PMID 11856371.
9. Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, et al. (August 2011). "Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma". Nature 476 (7360): 298–303. doi:10.1038/nature10351. PMC 3210554. PMID 21796119.
10. Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C, et al. (March 2012). "Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing". Proc. Natl. Acad. Sci. U.S.A. 109 (10): 3879–84. doi:10.1073/pnas.1121343109. PMC 3309757. PMID 22343534.
11. Farioli-Vecchioli S, Micheli L, Saraulli D, Ceccarelli M, Cannas S, Scardigli R, Leonardi L, Cinà I, Costanzi M, Ciotti MT, Moreira P, Rouault JP, Cestari V, Tirone F (2012). "Btg1 is Required to Maintain the Pool of Stem and Progenitor Cells of the Dentate Gyrus and Subventricular Zone". Front Neurosci 6: 124. doi:10.3389/fnins.2012.00124. PMC 3431174. PMID 22969701.
12. Tirone F, Farioli-Vecchioli S, Micheli L, Ceccarelli M, Leonardi L (2013). "Genetic control of adult neurogenesis: interplay of differentiation, proliferation and survival modulates new neurons function, and memory circuits". Front Cell Neurosci 7: 59. doi:10.3389/fncel.2013.00059. PMC 3653098. PMID 23734097.
13. Farioli-Vecchioli S, Mattera A, Micheli L, Ceccarelli M, Leonardi L, Saraulli D, Costanzi M, Cestari V, Rouault JP, Tirone F (2014). "Running rescues defective adult neurogenesis by shortening the length of the cell cycle of neural stem and progenitor cells". Stem cells. doi:10.1002/stem.1679.
14. Ceccarelli M, Micheli L, D'Andrea G, De Bardi M, Scheijen B, Ciotti M, Leonardi L, Luvisetto S, Tirone F (Dec 2015). "Altered cerebellum development and impaired motor coordination in mice lacking the Btg1 gene: Involvement of cyclin D1". Developmental Biology 408 (1): 109–25. doi:10.1016/j.ydbio.2015.10.007. PMID 26524254.

Further reading

• Rouault JP, Rimokh R, Tessa C, Paranhos G, Ffrench M, Duret L, Garoccio M, Germain D, Samarut J, Magaud JP (1992). "BTG1, a member of a new family of antiproliferative genes.". EMBO J. 11 (4): 1663–70. PMC 556617. PMID 1373383.
• Rimokh R, Rouault JP, Wahbi K, Gadoux M, Lafage M, Archimbaud E, Charrin C, Gentilhomme O, Germain D, Samarut J (1991). "A chromosome 12 coding region is juxtaposed to the MYC protooncogene locus in a t(8;12)(q24;q22) translocation in a case of B-cell chronic lymphocytic leukemia.". Genes Chromosomes Cancer 3 (1): 24–36. doi:10.1002/gcc.2870030106. PMID 2069907.
• Lin WJ, Gary JD, Yang MC, Clarke S, Herschman HR (1996). "The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase.". J. Biol. Chem. 271 (25): 15034–44. doi:10.1074/jbc.271.25.15034. PMID 8663146.
• Corjay MH, Kearney MA, Munzer DA, Diamond SM, Stoltenborg JK (1998). "Antiproliferative gene BTG1 is highly expressed in apoptotic cells in macrophage-rich areas of advanced lesions in Watanabe heritable hyperlipidemic rabbit and human.". Lab. Invest. 78 (7): 847–58. PMID 9690562.
• Bogdan JA, Adams-Burton C, Pedicord DL, Sukovich DA, Benfield PA, Corjay MH, Stoltenborg JK, Dicker IB (1999). "Human carbon catabolite repressor protein (CCR4)-associative factor 1: cloning, expression and characterization of its interaction with the B-cell translocation protein BTG1.". Biochem. J. 336. ( Pt 2): 471–81. PMC 1219893. PMID 9820826.
• Prévôt D, Voeltzel T, Birot AM, Morel AP, Rostan MC, Magaud JP, Corbo L (2000). "The leukemia-associated protein Btg1 and the p53-regulated protein Btg2 interact with the homeoprotein Hoxb9 and enhance its transcriptional activation.". J. Biol. Chem. 275 (1): 147–53. doi:10.1074/jbc.275.1.147. PMID 10617598.
• Prévôt D, Morel AP, Voeltzel T, Rostan MC, Rimokh R, Magaud JP, Corbo L (2001). "Relationships of the antiproliferative proteins BTG1 and BTG2 with CAF1, the human homolog of a component of the yeast CCR4 transcriptional complex: involvement in estrogen receptor alpha signaling pathway.". J. Biol. Chem. 276 (13): 9640–8. doi:10.1074/jbc.M008201200. PMID 11136725.
• Rodier A, Rochard P, Berthet C, Rouault JP, Casas F, Daury L, Busson M, Magaud JP, Wrutniak-Cabello C, Cabello G (2001). "Identification of functional domains involved in BTG1 cell localization.". Oncogene 20 (21): 2691–703. doi:10.1038/sj.onc.1204398. PMID 11420681.
• Yoshida Y, Hosoda E, Nakamura T, Yamamoto T (2001). "Association of ANA, a member of the antiproliferative Tob family proteins, with a Caf1 component of the CCR4 transcriptional regulatory complex.". Jpn. J. Cancer Res. 92 (6): 592–6. doi:10.1111/j.1349-7006.2001.tb01135.x. PMID 11429045.
• Berthet C, Guéhenneux F, Revol V, Samarut C, Lukaszewicz A, Dehay C, Dumontet C, Magaud JP, Rouault JP (2002). "Interaction of PRMT1 with BTG/TOB proteins in cell signalling: molecular analysis and functional aspects.". Genes Cells 7 (1): 29–39. doi:10.1046/j.1356-9597.2001.00497.x. PMID 11856371.
• Sasajima H, Nakagawa K, Yokosawa H (2002). "Antiproliferative proteins of the BTG/Tob family are degraded by the ubiquitin-proteasome system.". Eur. J. Biochem. 269 (14): 3596–604. doi:10.1046/j.1432-1033.2002.03052.x. PMID 12135500.
• Bakker WJ, Blázquez-Domingo M, Kolbus A, Besooyen J, Steinlein P, Beug H, Coffer PJ, Löwenberg B, von Lindern M, van Dijk TB (2004). "FoxO3a regulates erythroid differentiation and induces BTG1, an activator of protein arginine methyl transferase 1.". J. Cell Biol. 164 (2): 175–84. doi:10.1083/jcb.200307056. PMC 2172323. PMID 14734530.
• Busson M, Carazo A, Seyer P, Grandemange S, Casas F, Pessemesse L, Rouault JP, Wrutniak-Cabello C, Cabello G (2005). "Coactivation of nuclear receptors and myogenic factors induces the major BTG1 influence on muscle differentiation.". Oncogene 24 (10): 1698–710. doi:10.1038/sj.onc.1208373. PMID 15674337.