PMID- 18562694
OWN - NLM
STAT- MEDLINE
DCOM- 20090227
LR  - 20220317
IS  - 1939-4586 (Electronic)
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 19
IP  - 9
DP  - 2008 Sep
TI  - Transcriptional regulation of serine/threonine kinase-15 (STK15) expression by 
      hypoxia and HIF-1.
PG  - 3667-75
AB  - The serine/threonine kinase-15 (STK15) acts as a cell cycle regulator being 
      overexpressed in various tumors. One mechanism that could contribute to 
      overexpression of STK15 is tumor hypoxia where hypoxia-inducible factor-1 (HIF-1) 
      is a major regulator of transcription. Therefore, we analyzed whether hypoxia and 
      HIF-1 could contribute to overexpression of STK15. We found that hypoxia 
      increased STK15 expression and STK15 promoter activity in HepG2 tumor cells. 
      Overexpression of HIF-1 alpha induced STK15 gene transcription, whereas HIF-1 
      alpha siRNA and overexpression of prolyl hydroxylase 2 (PHD-2), a negative 
      regulator of HIF-1 alpha, reversed this effect. In addition, site-directed 
      mutagenesis experiments and chromatin immunoprecipitation revealed that from the 
      three putative hypoxia responsive elements (HRE) within the STK15 promoter only 
      HRE-2 was functional and bound HIF-1. Further, siRNA against STK15 inhibited 
      proliferation of HepG2 cells induced by hypoxia. These results show that STK15 
      gene transcription can be regulated by hypoxia and HIF-1 via HRE-2 of the STK15 
      promoter. Thus, tumor hypoxia may trigger overexpression of STK15 observed in 
      various tumors.
FAU - Klein, Alexandra
AU  - Klein A
AD  - Department of Biochemistry, Faculty of Chemistry, University of Kaiserslautern, 
      D-67663 Kaiserslautern, Germany.
FAU - Flugel, Daniela
AU  - Flugel D
FAU - Kietzmann, Thomas
AU  - Kietzmann T
LA  - eng
PT  - Journal Article
DEP - 20080618
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (RNA, Small Interfering)
RN  - EC 1.14.11.2 (EGLN1 protein, human)
RN  - EC 1.14.11.2 (Procollagen-Proline Dioxygenase)
RN  - EC 1.14.11.29 (Hypoxia-Inducible Factor-Proline Dioxygenases)
RN  - EC 2.7.11.1 (AURKA protein, human)
RN  - EC 2.7.11.1 (Aurora Kinase A)
RN  - EC 2.7.11.1 (Aurora Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Aurora Kinase A
MH  - Aurora Kinases
MH  - Carcinoma, Hepatocellular/metabolism
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - *Gene Expression Regulation, Enzymologic
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - *Hypoxia
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Hypoxia-Inducible Factor-Proline Dioxygenases
MH  - Oxygen/metabolism
MH  - Procollagen-Proline Dioxygenase/*metabolism
MH  - Promoter Regions, Genetic
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - RNA, Small Interfering/metabolism
MH  - *Transcription, Genetic
PMC - PMC2526712
EDAT- 2008/06/20 09:00
MHDA- 2009/02/28 09:00
PMCR- 2008/10/28
CRDT- 2008/06/20 09:00
PHST- 2008/06/20 09:00 [pubmed]
PHST- 2009/02/28 09:00 [medline]
PHST- 2008/06/20 09:00 [entrez]
PHST- 2008/10/28 00:00 [pmc-release]
AID - E08-01-0042 [pii]
AID - 3373081 [pii]
AID - 10.1091/mbc.e08-01-0042 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2008 Sep;19(9):3667-75. doi: 10.1091/mbc.e08-01-0042. Epub 2008 
      Jun 18.