1: Biochem J. 2005 Feb 15;386(Pt 1):63-72. 

The expression of the human neuronal alpha3 Na+,K+-ATPase subunit gene is
regulated by the activity of the Sp1 and NF-Y transcription factors.

Benfante R, Antonini RA, Vaccari M, Flora A, Chen F, Clementi F, Fornasari D.

Department of Pharmacology, School of Medicine, University of Milan, 32 via
Vanvitelli, 20129 Milan, Italy.

The Na+,K+-ATPase is a ubiquitous protein found in virtually all animal cells
which is involved in maintaining the electrochemical gradient across the plasma
membrane. It is a multimeric enzyme consisting of alpha, beta and gamma subunits
that may be present as different isoforms, each of which has a tissue-specific
expression profile. The expression of the Na+,K+-ATPase alpha3 subunit in humans
is confined to developing and adult brain and heart, thus suggesting that its
catalytic activity is strictly required in excitable tissues. In the present
study, we used structural, biochemical and functional criteria to analyse the
transcriptional mechanisms controlling the expression of the human gene in
neurons, and identified a minimal promoter region of approx. 100 bp upstream of
the major transcription start site which is capable of preferentially driving
the expression of a reporter gene in human neuronal cell lines. This region
contains the cognate DNA sites for the transcription factors Sp1/3/4
(transcription factors 1/3/4 purified from Sephacryl and phosphocellulose
columns), NF-Y (nuclear factor-Y) and a half CRE (cAMP-response element)-like
element that binds a still unknown protein. Although the expression of these
factors is not tissue-specific, co-operative functional interactions among them
are required to direct the activity of the promoter predominantly in neuronal
cells.

PMID: 15462673 [PubMed - indexed for MEDLINE]


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