Title

Transcriptional and translational regulation of connexin43 expression by estrogen

Date of Award

2000

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

First Committee Member

Rudolf Werner, Committee Chair

Abstract

Connexin43 (Cx43) is the major gap junction protein in the ventricle of the heart and in the uterus. In the heart, Cx43 is constitutively expressed but in the uterus it is only expressed prior to parturition enabling the muscle cells of the uterus to contract synchronously thereby expelling the fetus. Cx43 is upregulated in the myometrium by estrogen. There is good evidence that part of this regulation is transcriptional. However, Cx43 mRNA levels do not increase at the same rate as Cx43 protein suggesting a post-transcriptional component to this upregulation. The present study focuses on two promoter elements, a previously described activator site, and an AP1 site. Mutation analysis of these sites showed that only the activator site responds to estrogen whereas the AP I site, although not directly responsive to estrogen, participates in the maximal level achieved upon induction. In addition to these transcriptional elements, an Internal Ribosome Entry Site (IRES) was found to be the major determinant of translational efficiency. This site appears to be regulated by a second estrogen responsive element located in the 5 '-end of exon 1. The Cx43 IRES is also capable of allowing continued translation in a severe stress situation that inhibits cap-dependent translation. Cx43 is the second connexin gene in which an IRES has been found. This raises the intriguing possibility that connexin genes require continuous expression even in conditions where cap-mediated translation is inhibited such as severe stress, apoptosis, and mitosis.

Keywords

Biology, Molecular; Chemistry, Biochemistry

Link to Full Text

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