Upstream stimulatory factor regulates constitutive expression and hormonal suppression of the 90K (Mac-2BP) protein.

Abstract:

:We previously reported that hormones important for the normal growth and function of FRTL-5 rat thyroid cells, TSH, or its cAMP signal plus insulin or IGF-I, could transcriptionally suppress constitutive and gamma-interferon (IFN)-increased synthesis of the 90K protein (also known as Mac-2BP). Here we cloned the 5'-flanking region of the rat 90K gene and identified a minimal promoter containing an interferon response element and a consensus E-box or upstream stimulator factor (USF) binding site, which are highly conserved in both the human and murine genes. We show that suppression of constitutive and gamma-IFN-increased 90K gene expression by TSH/cAMP plus insulin/IGF-I depends on the ability of the hormones to decrease the binding of USF to the E-box, located upstream of the interferon response element. This site is required for the constitutive expression of the 90K gene. Transfection with USF1 and USF2 cDNAs increases constitutive promoter activity, attenuates the ability of TSH/cAMP plus insulin/IGF-I to decrease constitutive or gamma-IFN-increased 90K gene expression but does not abrogate the ability of gamma-IFN itself to increase 90K gene expression.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Grassadonia A,Tinari N,Fiorentino B,Nakazato M,Chung HK,Giuliani C,Napolitano G,Iacobelli S,Howcroft TK,Singer DS,Kohn LD,Consorzio Interuniversitario Nazionale per la Bioncologia.

doi

10.1210/en.2007-0024

subject

Has Abstract

pub_date

2007-07-01 00:00:00

pages

3507-17

issue

7

eissn

0013-7227

issn

1945-7170

pii

en.2007-0024

journal_volume

148

pub_type

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