FOXO1 cysteine-612 mediates stimulatory effects of the coregulators CBP and PGC1α on FOXO1 basal transcriptional activity

BHLHE40 and BHLHE41 (BHLHE40/41) are basic helix-loop-helix type transcription factors that play key roles in multiple cell behaviors. BHLHE40/41 were recently shown to be involved in an epithelial-to-mesenchymal transition (EMT). However, the precise mechanism of EMT control by BHLHE40/41 remains unclear. In the present study, we demonstrated that BHLHE40/41 expression was controlled in a pathological stage-dependent manner in human endometrial cancer (HEC). Ourin vitroassays showed that BHLHE40/41 suppressed tumor cell invasion. BHLHE40/41 also suppressed the transcription of the EMT effectorsSNAI1,SNAI2, andTWIST1. We identified the critical promoter regions ofTWIST1for its basal transcriptional activity. We elucidated that the transcription factor SP1 was involved in the basal transcriptional activity ofTWIST1and that BHLHE40/41 competed with SP1 for DNA binding to regulate gene transcription. This study is the first to report the detailed functions of BHLHE40 and BHLHE41 in the suppression of EMT effectorsin vitro. Our results suggest that BHLHE40/41 suppress tumor cell invasion by inhibiting EMT in tumor cells. We propose that BHLHE40/41 are promising markers to predict the aggressiveness of each HEC case and that molecular targeting strategies involving BHLHE40/41 and SP1 may effectively regulate HEC progression.

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The G1 Cyclin Cln3 Promotes Cell Cycle Entry via the Transcription Factor Swi6

Molecular and Cellular Biology ◽

10.1128/mcb.22.12.4402-4418.2002 ◽

2002 ◽

Vol 22 (12) ◽

pp. 4402-4418 ◽

Cited By ~ 62

Author(s):

Herman Wijnen ◽

Allison Landman ◽

Bruce Futcher

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Cycle ◽

Transcriptional Activity ◽

Leucine Zipper ◽

Stable Complex ◽

Amino Terminus ◽

Cyclin Dependent Kinase ◽

Cell Cycle Entry ◽

Basal Transcriptional Activity ◽

Commitment To Cell Division

ABSTRACT In Saccharomyces cerevisiae (budding yeast), commitment to cell division in late G1 is promoted by the G1 cyclin Cln3 and its associated cyclin-dependent kinase, Cdc28. We show here that all known aspects of the function of Cln3 in G1 phase, including control of cell size, pheromone sensitivity, cell cycle progress, and transcription, require the protein Swi6. Swi6 is a component of two related transcription factors, SBF and MBF, which are known to regulate many genes at the G1-S transition. The Cln3-Cdc28 complex somehow activates SBF and MBF, but there was no evidence for direct phosphorylation of SBF/MBF by Cln3-Cdc28 or for a stable complex between SBF/MBF and Cln3-Cdc28. The activation also does not depend on the ability of Cln3 to activate transcription when artificially recruited directly to a promoter. The amino terminus and the leucine zipper of Swi6 are important for the ability of Swi6 to respond to Cln3 but are not essential for the basal transcriptional activity of Swi6. Cln3-Cdc28 may activate SBF and MBF indirectly, perhaps by phosphorylating some intermediary protein.

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Differential binding of NF1-like nuclear factor to the mouse C4 and slp promoters as a major determinant of basal transcriptional activity

Molecular Immunology ◽

10.1016/0161-5890(93)90232-z ◽

1993 ◽

Vol 30 ◽

pp. 18

Author(s):

Z BUANG

Keyword(s):

Transcriptional Activity ◽

Major Determinant ◽

Nuclear Factor ◽

Differential Binding ◽

Basal Transcriptional Activity

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1288. Basal Transcriptional Activity of the Egr1 Promoter in Human Gliomas

Molecular Therapy ◽

10.1016/s1525-0016(16)44118-3 ◽

2002 ◽

Vol 5 (5) ◽

pp. S420

Keyword(s):

Transcriptional Activity ◽

Human Gliomas ◽

Basal Transcriptional Activity

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Transcriptional and posttranscriptional mechanisms regulate human renin gene expression in Calu-6 cells

AJP Renal Physiology ◽

10.1152/ajprenal.1996.271.1.f94 ◽

1996 ◽

Vol 271 (1) ◽

pp. F94-F100 ◽

Cited By ~ 6

Author(s):

J. A. Lang ◽

L. H. Ying ◽

B. J. Morris ◽

C. D. Sigmund

Keyword(s):

Transcriptional Activity ◽

De Novo ◽

Gene Transfection ◽

Fold Increase ◽

Regulatory Elements ◽

Human Renin ◽

Renin Gene ◽

A Cell ◽

Silencer Element ◽

Basal Transcriptional Activity

We have recently identified a human pulmonary carcinoma cell line (Calu-6) that expresses human renin (hREN) mRNA endogenously, and we use it herein as a model to examine the regulation of the hREN gene. Transfection analysis of a deletion series (-2750 to -149) of hREN promoter-luciferase fusion constructs revealed the presence of multiple weak regulatory elements within the first 1,301 bp of the 5'-flanking region and a classic silencer element within the first intron (intron A) of the gene. The 5'-flanking regulatory domain consisted of three closely linked elements, two negative and one positive, each contributing a cell-specific threefold modulation of transcriptional activity. Treating Calu-6 cells with forskolin caused a 100-fold increase in steady-state endogenous hREN mRNA but no increase in hREN promoter activity in transient transfections or in nuclear runoff transcription assays. Nevertheless, de novo transcription and translation were necessary for adenosine 3',5'-cyclic monophosphate (cAMP)-mediated induction. Our results suggest that multiple regulatory elements regulate basal transcriptional activity of the hREN gene and the increase in hREN mRNA by cAMP may be mediated by posttranscriptional mechanisms.

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