Transactivation activity

Hustert, E., et al., "Natural Protein Variants of Pregnane X Receptor with Altered Transactivation Activity Toward CYP3A4," Drug Metab. Dispos., 29, 1454—1459 (2001). 

Kim MY, Woo EM, Chong YT, Homenko DR, Kraus WL (2006) Acetylation of estrogen receptor alpha by p300 at lysines 266 and 268 enhances the DNA binding and transactivation activities of the receptor. Mol Endocrinol... 

More than 95% of the alterations in the p53 gene are point mutations that produce the mutant p53 protein, which in most cases has lost its transactivational activity, resulting in loss of tumor suppressor activity. p53 is the most commonly mutated gene in human cancers, and such a gene is involved in the development of at least 50% of clinical tumors (Damton, 1998). 

Flustert E, Zibat A, Presecan-Siedel E, Eiselt R, Mueller R, Fuss C, Brehm I, Brinkmann U, Eichelbaum M, Wojnowski L, Burk O. Natural protein variants of pregnane X receptor with altered transactivation activity toward CYP3A4. Drug Metab Dispos 2001 29 1454-1459. 

Engineered mutations in the second Cys-rich motif did not yield a consti-tutively active Mad. These results are consistent with the Cl motif being the major Cu-regulatory switch. Both Cys-rich motifs exhibited transactivation activity, although the Cl activator was weak relative to the C2 activator (Keller et al., 2000). Limited copper metalloregulation of Mad was observed with only the Cl activator fused to the N-terminal DNA-binding domain. Thus, the two Cys-rich motifs appear to function independently. The Cl Cys-rich motif appears to be a functional copper-regulatory domain, whereas the C2 motif is the major transactivator. 

Sang N, Fang J, Srinivas V, Leshchinsky I, Caro J. Carboxyl-terminal transactivation activity of hypoxia-inducible factor 1 alpha is governed by a von Hippel-Lindau protein-independent, hydroxylation-regulated association with p300/CBP. Mol. Cell. Biol. 2002 22 2984-2992. 

Abnet, C.C., R.L. Tanguay, W. Heideman and R.E. Peterson. Transactivation activity of human, zebrafish, and rainbow trout aryl hydrocarbon receptors expressed in COS-7 cells greater insight into species differences in toxic potency of polychlorinated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners. 

Kasten, M. and Giordano, A. (2001) CdklO, a Cdc2-related kinase, associates with the Ets2 transcription factor and modulates its transactivation activity. Oncogene, 20, 1832-1838. 

The functional consequence of PXR.2 has been briefly examined in cell-based assays. Compared to PXR, PXR.2 had marked reduction of basal and ligand (rifampin and corticosterone) induced transactivation activity of a CYP3A4 reporter in LS174 T cells [18], and, similarly, the orthologous mouse isoform mPXR.2 showed reduced response to ligands compared to mPXR. 1 [27]. Likewise, some of the UGT1 As (PXR targets) were induced by rifampin in Caco-2 cells transfected with PXR. 1 and PAR.2, but not with hPXR.2 [31]. 

PXR 10 G4374A Exon 4 V140M 50% lower protein in LSI74 T cells, increase in basal transactivation activity in LS174 T cells, reduced induction by Rif and corticosterone C = 0.002, AA = 0.0 [18]... 

SV23 characterized by a four amino acid insertion in the LBD adds an extra loop between helices 6 and 7. This isoform interacts weakly with CAR response elements and with various coactivators [61-65]. This variant was capable of transactivating CYP2B6 and MDR1 reporters in some studies but not CYP3A4 and IJGT1A1 reporters [61-65], Recently, it has been shown that upon RXRa overexpression SV23 shows RXR-dependent transactivation activity and interaction with SRC-1 as well as RXR-dependent response to clotrimazole and androstanol [66]. 

---