Reactome | ESR1:ESTG:P-TEFb recruited to paused RNA polymerase II on MYB gene

ESR1:ESTG:P-TEFb recruited to paused RNA polymerase II on MYB gene

Stable Identifier

R-HSA-9012315

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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ESR1:ESTG:P-TEFb recruited to paused RNA polymerase II on MYB gene

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MYB is frequently expressed in breast cancer and its expression is correlated with ER positive tumors (Guerin et al, 1990; Kauraniemi et al, 2000). MYB expression is estrogen-responsive, but hormone-dependent control is exerted at the level of transcriptional elongation rather than initiation (Frasor et al, 2003; Carroll et al, 2006; Bender et al, 1987; Watson et al, 1988; Drabsch et al, 2007). In the absence of estrogen, RNA polymerase II stalls at a stem-loop poly-T (SL-dT) tract between within intron 1 (Drabsch et al, 2007). Upon estrogen stimulation, a complex containing estrogen, the estrogen receptor and P-TEFb (an elongation factor consisting of Cyclin T and CDK9) is recruited to an ERE near the SL-dT. P-TEFb phosphorylates serine 2 in the RNA polymerase II CTD, allowing the polymerase to continue elongating (Drabsch et al, 2007; Mitra et al, 2012; reviewed in Gonda et al, 2008; Garriga and Grana, 2004). Although EREs have been identified around the SL-dT and have been shown by ChIP to be bound by ESR1, mutation of the EREs does not abrogate estrogen-responsive MYB expression, suggesting that the estrogen receptor either binds to a non-canonical site or it interacts through another transcription factor in this reaction (Drabsch et al, 2007; Mitra et al, 2012)

Literature References

PubMed ID	Title	Journal	Year
15276198	Cellular control of gene expression by T-type cyclin/CDK9 complexes Garriga, J, Grana, X	Gene	2004
17690249	Mechanism of and requirement for estrogen-regulated MYB expression in estrogen-receptor-positive breast cancer cells Drabsch, Y, Hugo, H, Zhang, R, Dowhan, DH, Miao, YR, Gewirtz, AM, Barry, SC, Ramsay, RG, Gonda, TJ	Proc. Natl. Acad. Sci. U.S.A.	2007
3498214	Differential expression of c-myb mRNA in murine B lymphomas by a block to transcription elongation Bender, TP, Thompson, CB, Kuehl, WM	Science	1987
2181374	Strong association between c-myb and oestrogen-receptor expression in human breast cancer Guérin, M, Sheng, ZM, Andrieu, N, Riou, G	Oncogene	1990
22492511	Estrogen receptor-α recruits P-TEFb to overcome transcriptional pausing in intron 1 of the MYB gene Mitra, P, Pereira, LA, Drabsch, Y, Ramsay, RG, Gonda, TJ	Nucleic Acids Res.	2012
3281094	A transcriptional arrest mechanism involved in controlling constitutive levels of mouse c-myb mRNA Watson, RJ	Oncogene	1988
18476782	Estrogen and MYB in breast cancer: potential for new therapies Gonda, TJ, Leo, P, Ramsay, RG	Expert Opin Biol Ther	2008
11034064	MYB oncogene amplification in hereditary BRCA1 breast cancer Kauraniemi, P, Hedenfalk, I, Persson, K, Duggan, DJ, Tanner, M, Johannsson, O, Olsson, H, Trent, JM, Isola, J, Borg, A	Cancer Res.	2000
17013392	Genome-wide analysis of estrogen receptor binding sites Carroll, JS, Meyer, CA, Song, J, Li, W, Geistlinger, TR, Eeckhoute, J, Brodsky, AS, Keeton, EK, Fertuck, KC, Hall, GF, Wang, Q, Bekiranov, S, Sementchenko, V, Fox, EA, Silver, PA, Gingeras, TR, Liu, XS, Brown, M	Nat. Genet.	2006
12959972	Profiling of estrogen up- and down-regulated gene expression in human breast cancer cells: insights into gene networks and pathways underlying estrogenic control of proliferation and cell phenotype Frasor, J, Danes, JM, Komm, B, Chang, KC, Lyttle, CR, Katzenellenbogen, BS	Endocrinology	2003