PMID- 11756548
OWN - NLM
STAT- MEDLINE
DCOM- 20020129
LR  - 20240410
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 22
IP  - 2
DP  - 2002 Jan
TI  - Genetic ablation of the steroid receptor coactivator-ubiquitin ligase, E6-AP, 
      results in tissue-selective steroid hormone resistance and defects in 
      reproduction.
PG  - 525-35
AB  - 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.
FAU - Smith, Carolyn L
AU  - Smith CL
AD  - Department of Molecular and Cellular Biology, Baylor College of Medicine, 
      Houston, Texas 77030-3498, USA. carolyns@bcm.tmc.edu
FAU - DeVera, Darryll G
AU  - DeVera DG
FAU - Lamb, Dolores J
AU  - Lamb DJ
FAU - Nawaz, Zafar
AU  - Nawaz Z
FAU - Jiang, Yong-Hui
AU  - Jiang YH
FAU - Beaudet, Arthur L
AU  - Beaudet AL
FAU - O'Malley, Bert W
AU  - O'Malley BW
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Receptors, Steroid)
RN  - 0 (Steroids)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (Ncoa1 protein, mouse)
RN  - EC 2.3.1.48 (Ncoa3 protein, mouse)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 3)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 6.- (Ligases)
SB  - IM
MH  - Animals
MH  - Drug Resistance
MH  - Female
MH  - Fertility/genetics/physiology
MH  - Gene Expression
MH  - Growth/genetics/physiology
MH  - Histone Acetyltransferases
MH  - Ligases/deficiency/*genetics/*physiology
MH  - Male
MH  - Mammary Glands, Animal/drug effects/growth & development
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nuclear Receptor Coactivator 1
MH  - Nuclear Receptor Coactivator 3
MH  - Pregnancy
MH  - Prostate/drug effects/growth & development
MH  - Receptors, Steroid/physiology
MH  - Reproduction/genetics/*physiology
MH  - Steroids/*pharmacology
MH  - Trans-Activators/deficiency/genetics/physiology
MH  - Transcription Factors/deficiency/genetics/physiology
MH  - Ubiquitin-Protein Ligases
PMC - PMC139730
EDAT- 2002/01/05 10:00
MHDA- 2002/01/30 10:01
PMCR- 2002/01/01
CRDT- 2002/01/05 10:00
PHST- 2002/01/05 10:00 [pubmed]
PHST- 2002/01/30 10:01 [medline]
PHST- 2002/01/05 10:00 [entrez]
PHST- 2002/01/01 00:00 [pmc-release]
AID - 0553 [pii]
AID - 10.1128/MCB.22.2.525-535.2002 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2002 Jan;22(2):525-35. doi: 10.1128/MCB.22.2.525-535.2002.