Protein BTG2

Apr 19, 2026 - 03:32
0 0
Protein BTG2

Link suggestions feature: 3 links added.

← Previous revision Revision as of 22:01, 18 April 2026
Line 5: Line 5:
The protein BTG2 is the human homolog of the PC3 (pheochromocytoma cell 3) protein in rat and of the Tis21 (tetradecanoyl phorbol acetate-inducible sequence 21) protein in mouse.{{cite journal | vauthors = Matsuda S, Rouault J, Magaud J, Berthet C | title = In search of a function for the TIS21/PC3/BTG1/TOB family | journal = FEBS Letters | volume = 497 | issue = 2–3 | pages = 67–72 | date = May 2001 | pmid = 11377414 | doi = 10.1016/S0014-5793(01)02436-X | doi-access = free | bibcode = 2001FEBSL.497...67M }}{{cite journal | vauthors = Tirone F | title = The gene PC3(TIS21/BTG2), prototype member of the PC3/BTG/TOB family: regulator in control of cell growth, differentiation, and DNA repair? | journal = Journal of Cellular Physiology | volume = 187 | issue = 2 | pages = 155–65 | date = May 2001 | pmid = 11267995 | doi = 10.1002/jcp.1062 | doi-access = free }} ''Tis21'' had been originally isolated as a sequence induced by [[12-O-Tetradecanoylphorbol-13-acetate|TPA]] in mouse fibroblasts, whereas ''PC3'' was originally isolated as sequence induced at the beginning of neuron differentiation; ''BTG2'' was then isolated in human cells as sequence induced by [[p53]] and DNA damage.{{cite web | title = Entrez Gene: BTG2 BTG family, member 2| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=7832}}
The protein BTG2 is the human homolog of the PC3 (pheochromocytoma cell 3) protein in rat and of the Tis21 (tetradecanoyl phorbol acetate-inducible sequence 21) protein in mouse.{{cite journal | vauthors = Matsuda S, Rouault J, Magaud J, Berthet C | title = In search of a function for the TIS21/PC3/BTG1/TOB family | journal = FEBS Letters | volume = 497 | issue = 2–3 | pages = 67–72 | date = May 2001 | pmid = 11377414 | doi = 10.1016/S0014-5793(01)02436-X | doi-access = free | bibcode = 2001FEBSL.497...67M }}{{cite journal | vauthors = Tirone F | title = The gene PC3(TIS21/BTG2), prototype member of the PC3/BTG/TOB family: regulator in control of cell growth, differentiation, and DNA repair? | journal = Journal of Cellular Physiology | volume = 187 | issue = 2 | pages = 155–65 | date = May 2001 | pmid = 11267995 | doi = 10.1002/jcp.1062 | doi-access = free }} ''Tis21'' had been originally isolated as a sequence induced by [[12-O-Tetradecanoylphorbol-13-acetate|TPA]] in mouse fibroblasts, whereas ''PC3'' was originally isolated as sequence induced at the beginning of neuron differentiation; ''BTG2'' was then isolated in human cells as sequence induced by [[p53]] and DNA damage.{{cite web | title = Entrez Gene: BTG2 BTG family, member 2| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=7832}}


The protein encoded by the gene BTG2 (which is the official name assigned to the gene PC3/Tis21/BTG2) is a member of the BTG/Tob family (that comprises six proteins [[BTG1]], BTG2/PC3/Tis21, [[BTG3]]/ANA, [[BTG4]]/PC3B, [[TOB1|Tob1]]/Tob and [[TOB2|Tob2]]).{{cite journal | vauthors = Winkler GS | title = The mammalian anti-proliferative BTG/Tob protein family | journal = Journal of Cellular Physiology | volume = 222 | issue = 1 | pages = 66–72 | date = January 2010 | pmid = 19746446 | doi = 10.1002/jcp.21919 | s2cid = 3436967 }} This family has structurally related proteins that appear to have antiproliferative properties. In particular, the BTG2 protein has been shown to negatively control a cell cycle checkpoint at the [[G1 phase|G1]] to [[S phase]] transition in fibroblasts and neuronal cells by direct inhibition of the activity of [[cyclin D1]] promoter.{{cite journal | vauthors = Montagnoli A, Guardavaccaro D, Starace G, Tirone F | title = Overexpression of the nerve growth factor-inducible PC3 immediate early gene is associated with growth inhibition | journal = Cell Growth & Differentiation | volume = 7 | issue = 10 | pages = 1327–36 | date = October 1996 | pmid = 8891336 | url = http://cgd.aacrjournals.org/cgi/content/abstract/7/10/1327 | access-date = 2010-03-16 | archive-date = 2015-05-18 | archive-url = https://web.archive.org/web/20150518091134/http://cgd.aacrjournals.org/cgi/content/abstract/7/10/1327 }}{{cite journal | vauthors = Guardavaccaro D, Corrente G, Covone F, Micheli L, D'Agnano I, Starace G, Caruso M, Tirone F | title = Arrest of G(1)-S progression by the p53-inducible gene PC3 is Rb dependent and relies on the inhibition of cyclin D1 transcription | journal = Molecular and Cellular Biology | volume = 20 | issue = 5 | pages = 1797–815 | date = March 2000 | pmid = 10669755 | pmc = 85361 | doi = 10.1128/MCB.20.5.1797-1815.2000 }}{{cite journal | vauthors = Farioli-Vecchioli S, Tanori M, Micheli L, Mancuso M, Leonardi L, Saran A, Ciotti MT, Ferretti E, Gulino A, Pazzaglia S, Tirone F | title = Inhibition of medulloblastoma tumorigenesis by the antiproliferative and pro-differentiative gene PC3 | journal = FASEB Journal | volume = 21 | issue = 9 | pages = 2215–25 | date = July 2007 | pmid = 17371797 | doi = 10.1096/fj.06-7548com | doi-access = free | s2cid = 4974360 | url = http://www.inmm.cnr.it/tirone/pdfs/PC3_inhibits_medulloblastoma.pdf}}
The protein encoded by the gene BTG2 (which is the official name assigned to the gene PC3/Tis21/BTG2) is a member of the BTG/Tob family (that comprises six proteins [[BTG1]], BTG2/PC3/Tis21, [[BTG3]]/ANA, [[BTG4]]/PC3B, [[TOB1|Tob1]]/Tob and [[TOB2|Tob2]]).{{cite journal | vauthors = Winkler GS | title = The mammalian anti-proliferative BTG/Tob protein family | journal = Journal of Cellular Physiology | volume = 222 | issue = 1 | pages = 66–72 | date = January 2010 | pmid = 19746446 | doi = 10.1002/jcp.21919 | s2cid = 3436967 }} This family has structurally related proteins that appear to have antiproliferative properties. In particular, the BTG2 protein has been shown to negatively control a [[cell cycle checkpoint]] at the [[G1 phase|G1]] to [[S phase]] transition in fibroblasts and neuronal cells by direct inhibition of the activity of [[cyclin D1]] promoter.{{cite journal | vauthors = Montagnoli A, Guardavaccaro D, Starace G, Tirone F | title = Overexpression of the nerve growth factor-inducible PC3 immediate early gene is associated with growth inhibition | journal = Cell Growth & Differentiation | volume = 7 | issue = 10 | pages = 1327–36 | date = October 1996 | pmid = 8891336 | url = http://cgd.aacrjournals.org/cgi/content/abstract/7/10/1327 | access-date = 2010-03-16 | archive-date = 2015-05-18 | archive-url = https://web.archive.org/web/20150518091134/http://cgd.aacrjournals.org/cgi/content/abstract/7/10/1327 }}{{cite journal | vauthors = Guardavaccaro D, Corrente G, Covone F, Micheli L, D'Agnano I, Starace G, Caruso M, Tirone F | title = Arrest of G(1)-S progression by the p53-inducible gene PC3 is Rb dependent and relies on the inhibition of cyclin D1 transcription | journal = Molecular and Cellular Biology | volume = 20 | issue = 5 | pages = 1797–815 | date = March 2000 | pmid = 10669755 | pmc = 85361 | doi = 10.1128/MCB.20.5.1797-1815.2000 }}{{cite journal | vauthors = Farioli-Vecchioli S, Tanori M, Micheli L, Mancuso M, Leonardi L, Saran A, Ciotti MT, Ferretti E, Gulino A, Pazzaglia S, Tirone F | title = Inhibition of medulloblastoma tumorigenesis by the antiproliferative and pro-differentiative gene PC3 | journal = FASEB Journal | volume = 21 | issue = 9 | pages = 2215–25 | date = July 2007 | pmid = 17371797 | doi = 10.1096/fj.06-7548com | doi-access = free | s2cid = 4974360 | url = http://www.inmm.cnr.it/tirone/pdfs/PC3_inhibits_medulloblastoma.pdf}}


== Regulator of neuron differentiation ==
== Regulator of neuron differentiation ==


A number of studies in vivo have shown that ''BTG2'' expression is associated with the neurogenic [[asymmetric cell division|asymmetric division]] in [[progenitor cell|neural progenitor cells]].{{cite journal | vauthors = Iacopetti P, Barsacchi G, Tirone F, Maffei L, Cremisi F | title = Developmental expression of PC3 gene is correlated with neuronal cell birthday | journal = Mechanisms of Development | volume = 47 | issue = 2 | pages = 127–37 | date = August 1994 | pmid = 7811636 | doi = 10.1016/0925-4773(94)90085-X | s2cid = 46597681 | url = http://gcpd.inmm.cnr.it/pdfs/PC3%20marker%20of%20newborn%20neurons%20-%20MechDev%201994.pdf | archive-url = https://web.archive.org/web/20110722030411/http://gcpd.inmm.cnr.it/pdfs/PC3%20marker%20of%20newborn%20neurons%20-%20MechDev%201994.pdf | archive-date = 2011-07-22 }}{{cite journal | vauthors = Iacopetti P, Michelini M, Stuckmann I, Oback B, Aaku-Saraste E, Huttner WB | title = Expression of the antiproliferative gene TIS21 at the onset of neurogenesis identifies single neuroepithelial cells that switch from proliferative to neuron-generating division | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 8 | pages = 4639–44 | date = April 1999 | pmid = 10200315 | pmc = 16385 | doi = 10.1073/pnas.96.8.4639 | bibcode = 1999PNAS...96.4639I | doi-access = free }}{{cite journal | vauthors = Haubensak W, Attardo A, Denk W, Huttner WB | title = Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 9 | pages = 3196–201 | date = March 2004 | pmid = 14963232 | pmc = 365766 | doi = 10.1073/pnas.0308600100 | doi-access = free }}{{cite journal | vauthors = Calegari F, Haubensak W, Haffner C, Huttner WB | title = Selective lengthening of the cell cycle in the neurogenic subpopulation of neural progenitor cells during mouse brain development | journal = The Journal of Neuroscience | volume = 25 | issue = 28 | pages = 6533–8 | date = July 2005 | pmid = 16014714 | pmc = 6725437 | doi = 10.1523/JNEUROSCI.0778-05.2005 }}{{cite journal | vauthors = Götz M, Huttner WB | title = The cell biology of neurogenesis | journal = Nature Reviews Molecular Cell Biology | volume = 6 | issue = 10 | pages = 777–88 | date = October 2005 | pmid = 16314867 | doi = 10.1038/nrm1739 | s2cid = 16955231 }} Tis21-GFP has been used as a neurogenic marker because it is not expressed until neurogenesis begins, is present in almost all early-born neurons, and interacts with neuron producing [[intermediate progenitor cell]]s.{{Cite journal|last1=Kowalczyk|first1=Tom|last2=Pontious|first2=Adria|last3=Englund|first3=Chris|last4=Daza|first4=Ray A. M.|last5=Bedogni|first5=Francesco|last6=Hodge|first6=Rebecca|last7=Attardo|first7=Alessio|last8=Bell|first8=Chris|last9=Huttner|first9=Wieland B.|date=2009-10-01|title=Intermediate Neuronal Progenitors (Basal Progenitors) Produce Pyramidal–Projection Neurons for All Layers of Cerebral Cortex|url= |journal=Cerebral Cortex|language=en|volume=19|issue=10|pages=2439–2450|doi=10.1093/cercor/bhn260|pmid=19168665|issn=1047-3211|pmc=2742596}} Moreover, when directly overexpressed in vivo in neural progenitor cells, BTG2 induces their differentiation.{{cite journal | vauthors = Canzoniere D, Farioli-Vecchioli S, Conti F, Ciotti MT, Tata AM, Augusti-Tocco G, Mattei E, Lakshmana MK, Krizhanovsky V, Reeves SA, Giovannoni R, Castano F, Servadio A, Ben-Arie N, Tirone F | title = Dual control of neurogenesis by PC3 through cell cycle inhibition and induction of Math1 | journal = The Journal of Neuroscience | volume = 24 | issue = 13 | pages = 3355–69 | date = March 2004 | pmid = 15056715 | pmc = 6730030 | doi = 10.1523/JNEUROSCI.3860-03.2004 }}{{cite journal | vauthors = Farioli-Vecchioli S, Saraulli D, Costanzi M, Pacioni S, Cinà I, Aceti M, Micheli L, Bacci A, Cestari V, Tirone F | title = The timing of differentiation of adult hippocampal neurons is crucial for spatial memory | journal = PLOS Biology | volume = 6 | issue = 10 | article-number = e246 | date = October 2008 | pmid = 18842068 | pmc = 2561078 | doi = 10.1371/journal.pbio.0060246 | doi-access = free }} In fact, in the neuronal PC12 cell line BTG2 is not able to trigger differentiation by itself, but only to synergize with NGF,{{cite journal | vauthors = Corrente G, Guardavaccaro D, Tirone F | title = PC3 potentiates NGF-induced differentiation and protects neurons from apoptosis | journal = NeuroReport | volume = 13 | issue = 4 | pages = 417–22 | date = March 2002 | pmid = 11930152 | doi = 10.1097/00001756-200203250-00011 | s2cid = 4996878 | url = http://www.inmm.cnr.it/tirone/pdfs/PC3-PC12-NGF%20-%20Neuroreport%202002.pdf }}{{cite journal | vauthors = el-Ghissassi F, Valsesia-Wittmann S, Falette N, Duriez C, Walden PD, Puisieux A | title = BTG2(TIS21/PC3) induces neuronal differentiation and prevents apoptosis of terminally differentiated PC12 cells | journal = Oncogene | volume = 21 | issue = 44 | pages = 6772–78 | date = October 2002 | pmid = 12360398 | doi = 10.1038/sj.onc.1205888 | doi-access = free }} while in vivo BTG2 is fully able to induce differentiation of progenitor cells, i.e., during embryonic development in the [[neuroblast]] of the neural tube and in [[granule cell|granule precursors]] of cerebellum, as well in adult progenitor cells of the [[dentate gyrus]] and of the [[subventricular zone]]. Notably, it has recently been shown that BTG2 is essential for the differentiation of new neurons, using a BTG2 [[gene knock out|knock out]] mouse.{{cite journal | vauthors = Farioli-Vecchioli S, Saraulli D, Costanzi M, Leonardi L, Cinà I, Micheli L, Nutini M, Longone P, Oh SP, Cestari V, Tirone F | title = Impaired terminal differentiation of hippocampal granule neurons and defective contextual memory in PC3/Tis21 knockout mice | journal = PLOS ONE | volume = 4 | issue = 12 | article-number = e8339 | date = December 2009 | pmid = 20020054 | pmc = 2791842 | doi = 10.1371/journal.pone.0008339 | bibcode = 2009PLoSO...4.8339F | doi-access = free }} BTG2 is thus a pan-neural gene required for the development of the new [[neuron]]s generated during adulthood, in the two neurogenic regions of adult brain, i.e., the [[hippocampus]] and the subventricular zone. Such requirement of BTG2 in neuron maturation is consistent with the fact that during brain development BTG2 is expressed in the proliferating neuroblasts of the ventricular zone of the neural tube, and to a lower extent in the differentiating neuroblasts of the mantle zone; postnatally it is expressed in cerebellar precursors mainly in the proliferating regions of the neuropithelium (i.e., in the external granular layer), and in the hippocampus in proliferating and differentiating progenitor cells. The pro-differentiative action of BTG2 appears to be consequent not only to inhibition of cell cycle progression but also to a BTG2-dependent activation of proneural genes in neural progenitor cells. In fact, BTG2 activates proneural genes by associating with the promoter of [[ID3 (gene)|Id3]], a key inhibitor of proneural gene activity, and by negatively regulating its activity.
A number of studies in vivo have shown that ''BTG2'' expression is associated with the neurogenic [[asymmetric cell division|asymmetric division]] in [[progenitor cell|neural progenitor cells]].{{cite journal | vauthors = Iacopetti P, Barsacchi G, Tirone F, Maffei L, Cremisi F | title = Developmental expression of PC3 gene is correlated with neuronal cell birthday | journal = Mechanisms of Development | volume = 47 | issue = 2 | pages = 127–37 | date = August 1994 | pmid = 7811636 | doi = 10.1016/0925-4773(94)90085-X | s2cid = 46597681 | url = http://gcpd.inmm.cnr.it/pdfs/PC3%20marker%20of%20newborn%20neurons%20-%20MechDev%201994.pdf | archive-url = https://web.archive.org/web/20110722030411/http://gcpd.inmm.cnr.it/pdfs/PC3%20marker%20of%20newborn%20neurons%20-%20MechDev%201994.pdf | archive-date = 2011-07-22 }}{{cite journal | vauthors = Iacopetti P, Michelini M, Stuckmann I, Oback B, Aaku-Saraste E, Huttner WB | title = Expression of the antiproliferative gene TIS21 at the onset of neurogenesis identifies single neuroepithelial cells that switch from proliferative to neuron-generating division | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 8 | pages = 4639–44 | date = April 1999 | pmid = 10200315 | pmc = 16385 | doi = 10.1073/pnas.96.8.4639 | bibcode = 1999PNAS...96.4639I | doi-access = free }}{{cite journal | vauthors = Haubensak W, Attardo A, Denk W, Huttner WB | title = Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 9 | pages = 3196–201 | date = March 2004 | pmid = 14963232 | pmc = 365766 | doi = 10.1073/pnas.0308600100 | doi-access = free }}{{cite journal | vauthors = Calegari F, Haubensak W, Haffner C, Huttner WB | title = Selective lengthening of the cell cycle in the neurogenic subpopulation of neural progenitor cells during mouse brain development | journal = The Journal of Neuroscience | volume = 25 | issue = 28 | pages = 6533–8 | date = July 2005 | pmid = 16014714 | pmc = 6725437 | doi = 10.1523/JNEUROSCI.0778-05.2005 }}{{cite journal | vauthors = Götz M, Huttner WB | title = The cell biology of neurogenesis | journal = Nature Reviews Molecular Cell Biology | volume = 6 | issue = 10 | pages = 777–88 | date = October 2005 | pmid = 16314867 | doi = 10.1038/nrm1739 | s2cid = 16955231 }} Tis21-GFP has been used as a neurogenic marker because it is not expressed until neurogenesis begins, is present in almost all early-born neurons, and interacts with neuron producing [[intermediate progenitor cell]]s.{{Cite journal|last1=Kowalczyk|first1=Tom|last2=Pontious|first2=Adria|last3=Englund|first3=Chris|last4=Daza|first4=Ray A. M.|last5=Bedogni|first5=Francesco|last6=Hodge|first6=Rebecca|last7=Attardo|first7=Alessio|last8=Bell|first8=Chris|last9=Huttner|first9=Wieland B.|date=2009-10-01|title=Intermediate Neuronal Progenitors (Basal Progenitors) Produce Pyramidal–Projection Neurons for All Layers of Cerebral Cortex|url= |journal=Cerebral Cortex|language=en|volume=19|issue=10|pages=2439–2450|doi=10.1093/cercor/bhn260|pmid=19168665|issn=1047-3211|pmc=2742596}} Moreover, when directly overexpressed in vivo in neural progenitor cells, BTG2 induces their differentiation.{{cite journal | vauthors = Canzoniere D, Farioli-Vecchioli S, Conti F, Ciotti MT, Tata AM, Augusti-Tocco G, Mattei E, Lakshmana MK, Krizhanovsky V, Reeves SA, Giovannoni R, Castano F, Servadio A, Ben-Arie N, Tirone F | title = Dual control of neurogenesis by PC3 through cell cycle inhibition and induction of Math1 | journal = The Journal of Neuroscience | volume = 24 | issue = 13 | pages = 3355–69 | date = March 2004 | pmid = 15056715 | pmc = 6730030 | doi = 10.1523/JNEUROSCI.3860-03.2004 }}{{cite journal | vauthors = Farioli-Vecchioli S, Saraulli D, Costanzi M, Pacioni S, Cinà I, Aceti M, Micheli L, Bacci A, Cestari V, Tirone F | title = The timing of differentiation of adult hippocampal neurons is crucial for spatial memory | journal = PLOS Biology | volume = 6 | issue = 10 | article-number = e246 | date = October 2008 | pmid = 18842068 | pmc = 2561078 | doi = 10.1371/journal.pbio.0060246 | doi-access = free }} In fact, in the neuronal PC12 cell line BTG2 is not able to trigger differentiation by itself, but only to synergize with NGF,{{cite journal | vauthors = Corrente G, Guardavaccaro D, Tirone F | title = PC3 potentiates NGF-induced differentiation and protects neurons from apoptosis | journal = NeuroReport | volume = 13 | issue = 4 | pages = 417–22 | date = March 2002 | pmid = 11930152 | doi = 10.1097/00001756-200203250-00011 | s2cid = 4996878 | url = http://www.inmm.cnr.it/tirone/pdfs/PC3-PC12-NGF%20-%20Neuroreport%202002.pdf }}{{cite journal | vauthors = el-Ghissassi F, Valsesia-Wittmann S, Falette N, Duriez C, Walden PD, Puisieux A | title = BTG2(TIS21/PC3) induces neuronal differentiation and prevents apoptosis of terminally differentiated PC12 cells | journal = Oncogene | volume = 21 | issue = 44 | pages = 6772–78 | date = October 2002 | pmid = 12360398 | doi = 10.1038/sj.onc.1205888 | doi-access = free }} while in vivo BTG2 is fully able to induce differentiation of progenitor cells, i.e., during embryonic development in the [[neuroblast]] of the [[neural tube]] and in [[granule cell|granule precursors]] of cerebellum, as well in adult progenitor cells of the [[dentate gyrus]] and of the [[subventricular zone]]. Notably, it has recently been shown that BTG2 is essential for the differentiation of new neurons, using a BTG2 [[gene knock out|knock out]] mouse.{{cite journal | vauthors = Farioli-Vecchioli S, Saraulli D, Costanzi M, Leonardi L, Cinà I, Micheli L, Nutini M, Longone P, Oh SP, Cestari V, Tirone F | title = Impaired terminal differentiation of hippocampal granule neurons and defective contextual memory in PC3/Tis21 knockout mice | journal = PLOS ONE | volume = 4 | issue = 12 | article-number = e8339 | date = December 2009 | pmid = 20020054 | pmc = 2791842 | doi = 10.1371/journal.pone.0008339 | bibcode = 2009PLoSO...4.8339F | doi-access = free }} BTG2 is thus a pan-neural gene required for the development of the new [[neuron]]s generated during adulthood, in the two neurogenic regions of adult brain, i.e., the [[hippocampus]] and the subventricular zone. Such requirement of BTG2 in neuron maturation is consistent with the fact that during brain development BTG2 is expressed in the proliferating neuroblasts of the ventricular zone of the neural tube, and to a lower extent in the differentiating neuroblasts of the [[mantle zone]]; postnatally it is expressed in cerebellar precursors mainly in the proliferating regions of the neuropithelium (i.e., in the external granular layer), and in the hippocampus in proliferating and differentiating progenitor cells. The pro-differentiative action of BTG2 appears to be consequent not only to inhibition of cell cycle progression but also to a BTG2-dependent activation of proneural genes in neural progenitor cells. In fact, BTG2 activates proneural genes by associating with the promoter of [[ID3 (gene)|Id3]], a key inhibitor of proneural gene activity, and by negatively regulating its activity.


BTG2 is a transcriptional cofactor, given that it has been shown to associate with, and regulate the promoters not only of Id3 but also of [[cyclin D1]] and [[retinoic acid receptor beta|RAR-β]], being part of transcriptional complexes.{{cite journal | vauthors = Passeri D, Marcucci A, Rizzo G, Billi M, Panigada M, Leonardi L, Tirone F, Grignani F | title = Btg2 enhances retinoic acid-induced differentiation by modulating histone H4 methylation and acetylation | journal = Molecular and Cellular Biology | volume = 26 | issue = 13 | pages = 5023–32 | date = July 2006 | pmid = 16782888 | pmc = 1489145 | doi = 10.1128/MCB.01360-05 }}{{cite journal | vauthors = Lin WJ, Gary JD, Yang MC, Clarke S, Herschman HR | title = The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase | journal = The Journal of Biological Chemistry | volume = 271 | issue = 25 | pages = 15034–44 | date = June 1996 | pmid = 8663146 | doi = 10.1074/jbc.271.25.15034 | doi-access = free }} It has been shown that when the differentiation of new neurons of the hippocampus - a brain region important for learning and memory - is either accelerated or delayed by means of overexpression or deletion of BTG2, respectively, spatial and contextual memory is heavily altered. This suggests that the time the young neurons spend in different states of neuronal differentiation is critical for their ultimate function in learning and memory, and that BTG2 may play a role in the timing of recruitment of the new neuron into memory circuits.
BTG2 is a transcriptional cofactor, given that it has been shown to associate with, and regulate the promoters not only of Id3 but also of [[cyclin D1]] and [[retinoic acid receptor beta|RAR-β]], being part of transcriptional complexes.{{cite journal | vauthors = Passeri D, Marcucci A, Rizzo G, Billi M, Panigada M, Leonardi L, Tirone F, Grignani F | title = Btg2 enhances retinoic acid-induced differentiation by modulating histone H4 methylation and acetylation | journal = Molecular and Cellular Biology | volume = 26 | issue = 13 | pages = 5023–32 | date = July 2006 | pmid = 16782888 | pmc = 1489145 | doi = 10.1128/MCB.01360-05 }}{{cite journal | vauthors = Lin WJ, Gary JD, Yang MC, Clarke S, Herschman HR | title = The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase | journal = The Journal of Biological Chemistry | volume = 271 | issue = 25 | pages = 15034–44 | date = June 1996 | pmid = 8663146 | doi = 10.1074/jbc.271.25.15034 | doi-access = free }} It has been shown that when the differentiation of new neurons of the hippocampus - a brain region important for learning and memory - is either accelerated or delayed by means of overexpression or deletion of BTG2, respectively, spatial and contextual memory is heavily altered. This suggests that the time the young neurons spend in different states of neuronal differentiation is critical for their ultimate function in learning and memory, and that BTG2 may play a role in the timing of recruitment of the new neuron into memory circuits.
Read More