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]
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 sub ventricular zone (see for review[11]). In particular, BTG1 keeps adult neural stem cells in quiescence, preserving the neural stem cells pool from depletion. In the absence of BTG1, the stem and progenitor cells initially hyper proliferate and then in the longer period lose the ability to proliferate and expand.[12][13] 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.[14][15]
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.[16]
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.[13]
References
↑Iwai K, Hirata K, Ishida T, Takeuchi S, Hirase T, Rikitake Y, et al. (April 2004). "An anti-proliferative gene BTG1 regulates angiogenesis in vitro". Biochemical and Biophysical Research Communications. 316 (3): 628–35. doi:10.1016/j.bbrc.2004.02.095. PMID15033446.
↑ 4.04.1Prévôt D, Morel AP, Voeltzel T, Rostan MC, Rimokh R, Magaud JP, et al. (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". The Journal of Biological Chemistry. 276 (13): 9640–8. doi:10.1074/jbc.M008201200. PMID11136725.
↑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. PMID16189514.
↑Prévôt D, Voeltzel T, Birot AM, Morel AP, Rostan MC, Magaud JP, et al. (January 2000). "The leukemia-associated protein Btg1 and the p53-regulated protein Btg2 interact with the homeoprotein Hoxb9 and enhance its transcriptional activation". The Journal of Biological Chemistry. 275 (1): 147–53. doi:10.1074/jbc.275.1.147. PMID10617598.
↑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". The Journal of Biological Chemistry. 271 (25): 15034–44. doi:10.1074/jbc.271.25.15034. PMID8663146.
↑Berthet C, Guéhenneux F, Revol V, Samarut C, Lukaszewicz A, Dehay C, et al. (January 2002). "Interaction of PRMT1 with BTG/TOB proteins in cell signalling: molecular analysis and functional aspects". Genes to Cells. 7 (1): 29–39. doi:10.1046/j.1356-9597.2001.00497.x. PMID11856371.
↑Farioli-Vecchioli S, Mattera A, Micheli L, Ceccarelli M, Leonardi L, Saraulli D, et al. (July 2014). "Running rescues defective adult neurogenesis by shortening the length of the cell cycle of neural stem and progenitor cells". Stem Cells. 32 (7): 1968–82. doi:10.1002/stem.1679. PMID24604711.
↑Ceccarelli M, Micheli L, D'Andrea G, De Bardi M, Scheijen B, Ciotti M, et al. (December 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. PMID26524254.
Rimokh R, Rouault JP, Wahbi K, Gadoux M, Lafage M, Archimbaud E, et al. (January 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. PMID2069907.
Corjay MH, Kearney MA, Munzer DA, Diamond SM, Stoltenborg JK (July 1998). "Antiproliferative gene BTG1 is highly expressed in apoptotic cells in macrophage-rich areas of advanced lesions in Watanabe heritable hyperlipidemic rabbit and human". Laboratory Investigation; A Journal of Technical Methods and Pathology. 78 (7): 847–58. PMID9690562.
Prévôt D, Voeltzel T, Birot AM, Morel AP, Rostan MC, Magaud JP, et al. (January 2000). "The leukemia-associated protein Btg1 and the p53-regulated protein Btg2 interact with the homeoprotein Hoxb9 and enhance its transcriptional activation". The Journal of Biological Chemistry. 275 (1): 147–53. doi:10.1074/jbc.275.1.147. PMID10617598.
Prévôt D, Morel AP, Voeltzel T, Rostan MC, Rimokh R, Magaud JP, et al. (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". The Journal of Biological Chemistry. 276 (13): 9640–8. doi:10.1074/jbc.M008201200. PMID11136725.
Rodier A, Rochard P, Berthet C, Rouault JP, Casas F, Daury L, et al. (May 2001). "Identification of functional domains involved in BTG1 cell localization". Oncogene. 20 (21): 2691–703. doi:10.1038/sj.onc.1204398. PMID11420681.
Yoshida Y, Hosoda E, Nakamura T, Yamamoto T (June 2001). "Association of ANA, a member of the antiproliferative Tob family proteins, with a Caf1 component of the CCR4 transcriptional regulatory complex". Japanese Journal of Cancer Research. 92 (6): 592–6. doi:10.1111/j.1349-7006.2001.tb01135.x. PMID11429045.
Berthet C, Guéhenneux F, Revol V, Samarut C, Lukaszewicz A, Dehay C, et al. (January 2002). "Interaction of PRMT1 with BTG/TOB proteins in cell signalling: molecular analysis and functional aspects". Genes to Cells. 7 (1): 29–39. doi:10.1046/j.1356-9597.2001.00497.x. PMID11856371.
Sasajima H, Nakagawa K, Yokosawa H (July 2002). "Antiproliferative proteins of the BTG/Tob family are degraded by the ubiquitin-proteasome system". European Journal of Biochemistry / FEBS. 269 (14): 3596–604. doi:10.1046/j.1432-1033.2002.03052.x. PMID12135500.
Busson M, Carazo A, Seyer P, Grandemange S, Casas F, Pessemesse L, et al. (March 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. PMID15674337.