| First Author | Smith CL | Year | 2002 |
| Journal | Mol Cell Biol | Volume | 22 |
| Issue | 2 | Pages | 525-35 |
| PubMed ID | 11756548 | Mgi Jnum | J:99980 |
| Mgi Id | MGI:3584321 | Doi | 10.1128/MCB.22.2.525-535.2002 |
| Citation | Smith CL, et al. (2002) Genetic ablation of the steroid receptor coactivator-ubiquitin ligase, E6-AP, results in tissue-selective steroid hormone resistance and defects in reproduction. Mol Cell Biol 22(2):525-35 |
| abstractText | The E6-associated protein (E6-AP), although originally identified as a ubiquitin ligase, has recently been shown to function as a coactivator of steroid receptor-dependent gene expression in in vitro assays. In order to determine whether E6-AP acts as a coactivator in vivo, physiological parameters associated with male and female sex steroid action were assessed in the E6-AP null mouse. Gonadal size was reduced in E6-AP null male and female mice in comparison to wild-type controls in conjunction with reduced fertility in both genders. Consistent with this observation, defects in sperm production and function, as well as ovulation were observed. In comparison to wild-type controls, induction of prostate gland growth induced by testosterone and uterine growth by estradiol were significantly reduced. In contrast, estrogen and progesterone-stimulated growth of virgin mammary gland was not compromised by E6-AP ablation despite E6-AP expression in this tissue. This latter finding contrasts with the impaired estrogen and progesterone-induced mammary gland development observed previously for steroid receptor coactivator type 1 (SRC-1) and SRC-3 female knockout mice. Taken together, these results are consistent with a role for E6-AP in mediating a subset of steroid hormone actions in vivo. Nevertheless, differences observed between SRC and E6-AP knockout phenotypes indicate that these two families of steroid receptor coactivators are not functionally equivalent and supports the hypothesis that coactivators contribute to tissue-specific steroid hormone action. |
