Differential regulation of serum- and glucocorticoid-inducible kinase 1 (SGK1) splice variants based on alternative initiation of transcription

Autoren

Perikles Simon
Michaela Schneck
Tabea Hochstetter
Evgenia Koutsouki
Michel Mittelbronn
Axel Merseburger
Cora Weigert
Andreas Niess
Florian Lang

DOI

10.1159/000110432

eISSN

1421-9778

ISSN

1015-8987

Ausgabe der Veröffentlichung

6

Zeitschrift

Cellular Physiology and Biochemistry

Sprache

en

Online publication date

2007

Paginierung

715 - 728

Datum der Veröffentlichung

2007

Status

Published

Herausgeber

S. Karger AG

Herausgeber URL

http://dx.doi.org/10.1159/000110432

Datum der Datenerfassung

2023

Titel

Differential Regulation of Serum- and Glucocorticoid-Inducible Kinase 1 (SGK1) Splice Variants Based on Alternative Initiation of Transcription

Ausgabe der Zeitschrift

20

Datenquelle: Crossref

Abstract

The serum- and glucocorticoid-inducible kinase 1 (SGK1) is a key-regulator of transport, cell volume and cell survival. SGK1 transcription is under genomic control of a wide variety of hormones and cell stressors. Little is known, however, about sequence variation in SGK1 transcripts. Thus, we took an in silico approach to determine sequence variations in the N-terminal region of SGK1, which is considered particularly important for subcellular SGK1 localization. Expressed Sequence Tag analysis revealed two novel phylogenetically highly conserved SGK1 mRNAs with different promoter sites based on alternative initiation of transcription at -2981, -850 upstream of the transcription initiation site (+1) of the reference mRNA. RT-PCR in various human cell lines and tissues confirmed the expression of the 3 alternative splice variants, which differed exclusively in their first exons. The two novel variants were devoid of the localization and degradation signal with otherwise unchanged and intact open reading frames. Spatial distribution of transcription factor binding sites among the three promoter sites indicated common responsiveness to glucocorticoids but different responsiveness to hypoxia and cellular differentiation. Differential expression under those conditions was confirmed for all variants in cultured myoblasts and myotubes. p53 and ETF-1 binding sites were overrepresented at the promoter site of the reference sequence variant SGK1(+1). Transcript levels were 4.1-fold [SGK1(+1)] and 3.1-fold [SGK1(-850)] higher in renal clear cell carcinoma than in remote tissue. The transcript levels were 42-fold [SGK1(+1)], 26-fold [SGK1(-850)] and 17-fold [SGK1(-2981)] higher in highly malignant human glioma cells than in non-neoplastic brain tissue. SGK1 transcript levels were differentially increased by differentiation or hypoxia (treatment with CoCl(2)). In conclusion, the present observations disclose the transcription of three distinct SGK1 splice variants, which are all markedly upregulated in tumor tissue but differentially upregulated following differentiation or hypoxia.

Addresses

Medical Clinic, Department of Sports Medicine, University of Tuebingen, Tuebingen (Germany).

Autoren

Perikles Simon
Michaela Schneck
Tabea Hochstetter
Evgenia Koutsouki
Michel Mittelbronn
Axel Merseburger
Cora Weigert
Andreas Niess
Florian Lang

DOI

10.1159/000110432

eISSN

1421-9778

Externe Identifier

PubMed Identifier: 17982254

Open access

false

ISSN

1015-8987

Ausgabe der Veröffentlichung

6

Zeitschrift

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology

Schlüsselwörter

Cell Line, Tumor
Chromosomes, Human, Pair 16
Myoblasts
Humans
Carcinoma, Renal Cell
Kidney Neoplasms
Cobalt
Immediate-Early Proteins
Transcription Factors
RNA, Messenger
Sequence Analysis, DNA
Computational Biology
Cell Differentiation
Transcription, Genetic
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Alternative Splicing
Up-Regulation
Binding Sites
Amino Acid Sequence
Time Factors
Molecular Sequence Data
Promoter Regions, Genetic
Protein Serine-Threonine Kinases

Sprache

eng

Medium

Print

Paginierung

715 - 728

Datum der Veröffentlichung

2007

Status

Published

Datum der Datenerfassung

2007

Titel

Differential regulation of serum- and glucocorticoid-inducible kinase 1 (SGK1) splice variants based on alternative initiation of transcription.

Sub types

Journal Article

Ausgabe der Zeitschrift

20

Datenquelle: Europe PubMed Central

Abstract

The serum- and glucocorticoid-inducible kinase 1 (SGK1) is a key-regulator of transport, cell volume and cell survival. SGK1 transcription is under genomic control of a wide variety of hormones and cell stressors. Little is known, however, about sequence variation in SGK1 transcripts. Thus, we took an in silico approach to determine sequence variations in the N-terminal region of SGK1, which is considered particularly important for subcellular SGK1 localization. Expressed Sequence Tag analysis revealed two novel phylogenetically highly conserved SGK1 mRNAs with different promoter sites based on alternative initiation of transcription at -2981, -850 upstream of the transcription initiation site (+1) of the reference mRNA. RT-PCR in various human cell lines and tissues confirmed the expression of the 3 alternative splice variants, which differed exclusively in their first exons. The two novel variants were devoid of the localization and degradation signal with otherwise unchanged and intact open reading frames. Spatial distribution of transcription factor binding sites among the three promoter sites indicated common responsiveness to glucocorticoids but different responsiveness to hypoxia and cellular differentiation. Differential expression under those conditions was confirmed for all variants in cultured myoblasts and myotubes. p53 and ETF-1 binding sites were overrepresented at the promoter site of the reference sequence variant SGK1(+1). Transcript levels were 4.1-fold [SGK1(+1)] and 3.1-fold [SGK1(-850)] higher in renal clear cell carcinoma than in remote tissue. The transcript levels were 42-fold [SGK1(+1)], 26-fold [SGK1(-850)] and 17-fold [SGK1(-2981)] higher in highly malignant human glioma cells than in non-neoplastic brain tissue. SGK1 transcript levels were differentially increased by differentiation or hypoxia (treatment with CoCl(2)). In conclusion, the present observations disclose the transcription of three distinct SGK1 splice variants, which are all markedly upregulated in tumor tissue but differentially upregulated following differentiation or hypoxia.

Date of acceptance

2007

Autoren

Perikles Simon
Michaela Schneck
Tabea Hochstetter
Evgenia Koutsouki
Michel Mittelbronn
Axel Merseburger
Cora Weigert
Andreas Niess
Florian Lang

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/17982254

DOI

10.1159/000110432

ISSN

1015-8987

Ausgabe der Veröffentlichung

6

Zeitschrift

Cell Physiol Biochem

Schlüsselwörter

Alternative Splicing
Amino Acid Sequence
Binding Sites
Carcinoma, Renal Cell
Cell Differentiation
Cell Line, Tumor
Chromosomes, Human, Pair 16
Cobalt
Computational Biology
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Humans
Immediate-Early Proteins
Kidney Neoplasms
Molecular Sequence Data
Myoblasts
Promoter Regions, Genetic
Protein Serine-Threonine Kinases
RNA, Messenger
Sequence Analysis, DNA
Time Factors
Transcription Factors
Transcription, Genetic
Up-Regulation

Sprache

eng

Country

Germany

Paginierung

715 - 728

PII

110432

Datum der Veröffentlichung

2007

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2007

Titel

Differential regulation of serum- and glucocorticoid-inducible kinase 1 (SGK1) splice variants based on alternative initiation of transcription.

Sub types

Journal Article

Ausgabe der Zeitschrift

20

Datenquelle: PubMed

Differential regulation of serum- and glucocorticoid-inducible kinase 1 (SGK1) splice variants based on alternative initiation of transcription

Werkzeuge