Brd4 and HEXIM1: multiple roles in P-TEFb regulation and cancer - PubMed (original) (raw)

Review

Brd4 and HEXIM1: multiple roles in P-TEFb regulation and cancer

Ruichuan Chen et al. Biomed Res Int. 2014.

Abstract

Bromodomain-containing protein 4 (Brd4) and hexamethylene bisacetamide (HMBA) inducible protein 1 (HEXIM1) are two opposing regulators of the positive transcription elongation factor b (P-TEFb), which is the master modulator of RNA polymerase II during transcriptional elongation. While Brd4 recruits P-TEFb to promoter-proximal chromatins to activate transcription, HEXIM1 sequesters P-TEFb into an inactive complex containing the 7SK small nuclear RNA. Besides regulating P-TEFb's transcriptional activity, recent evidence demonstrates that both Brd4 and HEXIM1 also play novel roles in cell cycle progression and tumorigenesis. Here we will discuss the current knowledge on Brd4 and HEXIM1 and their implication as novel therapeutic options against cancer.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Regulation of P-TEFb activity by its positive regulator HEXIM1 and negative regulator Brd4.

Figure 2

Figure 2

Regulation of the association between Brd4 and chromatins in the nonstimulated (a) and stimulated (b) cells.

Figure 3

Figure 3

Alignment of the HDM2 ubiquitination sites between p53 (amino acids 370–386) and HEXIM1 (amino acids 150–161). The HDM2-ubiquitinated lysine residues are indicated in black boxes.

Figure 4

Figure 4

HEXIM1 stabilizes p53 by blocking the HDM2-mediated ubiquitination of p53. Human p53 protein can be divided into five domains: transactivation (TA), proline rich (PR), DNA binding (DB), oligomerization (OLI), and negative (NEG) domains. The HDM2 ubiquitination sites are located with the NEG domain. HEXIM1 interacts with the NEG domain of p53 and prevents the binding between p53 and HDM2.

Similar articles

Cited by

References

    1. Marshall NF, Price DH. Purification of P-TEFb, a transcription factor required for the transition into productive elongation. The Journal of Biological Chemistry. 1995;270(21):12335–12338. - PubMed
    1. Henriques T, Gilchrist DA, Nechaev S, et al. Stable pausing by RNA polymerase II provides an opportunity to target and integrate regulatory signals. Molecular Cell. 2013;52(4):517–528. - PMC - PubMed
    1. Wada T, Takagi T, Yamaguchi Y, Watanabe D, Handa H. Evidence that P-TEFb alleviates the negative effect of DSIF on RNA polymerase II-dependent transcription in vitro. The EMBO Journal. 1998;17(24):7395–7403. - PMC - PubMed
    1. Yamaguchi Y, Takagi T, Wada T, et al. NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation. Cell. 1999;97(1):41–51. - PubMed
    1. Cheng B, Li T, Rahl PB, et al. Functional association of gdown1 with RNA polymerase II poised on human genes. Molecular Cell. 2012;45(1):38–50. - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources