PMID- 22172574
OWN - NLM
STAT- MEDLINE
DCOM- 20120411
LR  - 20211021
IS  - 1521-0111 (Electronic)
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 81
IP  - 3
DP  - 2012 Mar
TI  - Specificity protein 1 (sp1) oscillation is involved in copper homeostasis 
      maintenance by regulating human high-affinity copper transporter 1 expression.
PG  - 455-64
LID - 10.1124/mol.111.076422 [doi]
AB  - Copper is an essential micronutrient for cell growth but is toxic in excess. 
      Copper transporter (Ctr1) plays an important role in regulating adequate copper 
      levels in mammalian cells. We have shown previously that expression of the human 
      high-affinity copper transporter (hCtr1) was transcriptionally up-regulated under 
      copper-depleted conditions and down-regulated under replete conditions; moreover, 
      elevated hCtr1 levels suppress hCtr1 expression. Specificity protein 1 (Sp1) 
      regulates expression of hCtr1 under copper-stressed conditions. In this study, we 
      made the following important observations: 1) Sp1 expression is down-regulated 
      under copper-replete conditions but up-regulated under copper-depleted 
      conditions. These up- and down-regulations of Sp1 in turn regulate hCtr1 
      expression to control copper homeostasis. 2) Copper-regulated Sp1 expression 
      involved Sp1 binding to its own promoter as demonstrated by the chromatin 
      immunoprecipitation assay; therefore, Sp1 is also transcriptionally 
      self-regulated via hCtr1/copper intermediation. 3) Both zinc finger and 
      glutamine-rich transactivation domains of Sp1 are involved in the Sp1-mediated 
      hCtr1 and Sp1 regulation by copper stresses. 4) Although Sp3 expression is also 
      regulated by copper availability, Sp3 does not regulate hCtr1 homeostasis. 
      Collectively, our results demonstrated that mammalian cells use Sp1 oscillation 
      in response to copper availability to regulate copper homeostasis through hCtr1 
      expression in a tripartite inter-regulatory relationship. These findings have 
      important implications in mammalian copper physiology regulation.
FAU - Liang, Zheng D
AU  - Liang ZD
AD  - Department of Molecular Pathology, The University of Texas MD Anderson Cancer 
      Center, Houston, TX 77054, USA.
FAU - Tsai, Wen-Bin
AU  - Tsai WB
FAU - Lee, Mei-Yi
AU  - Lee MY
FAU - Savaraj, Niramol
AU  - Savaraj N
FAU - Kuo, Macus Tien
AU  - Kuo MT
LA  - eng
GR  - R01 CA149260/CA/NCI NIH HHS/United States
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - R01-CA149620/CA/NCI NIH HHS/United States
GR  - CA16672/CA/NCI NIH HHS/United States
GR  - R01 CA152197/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20111215
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Cation Transport Proteins)
RN  - 0 (Copper Transporter 1)
RN  - 0 (Sp1 Transcription Factor)
RN  - 789U1901C5 (Copper)
SB  - IM
MH  - Blotting, Western
MH  - Cation Transport Proteins/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Chromatin Immunoprecipitation
MH  - Copper/*metabolism
MH  - Copper Transporter 1
MH  - Down-Regulation
MH  - Homeostasis/*physiology
MH  - Humans
MH  - Immunohistochemistry
MH  - Sp1 Transcription Factor/*physiology
MH  - Transcription, Genetic
MH  - Up-Regulation
MH  - Zinc Fingers
PMC - PMC3286298
EDAT- 2011/12/17 06:00
MHDA- 2012/04/12 06:00
PMCR- 2013/03/01
CRDT- 2011/12/17 06:00
PHST- 2011/12/17 06:00 [entrez]
PHST- 2011/12/17 06:00 [pubmed]
PHST- 2012/04/12 06:00 [medline]
PHST- 2013/03/01 00:00 [pmc-release]
AID - mol.111.076422 [pii]
AID - 3751799 [pii]
AID - 10.1124/mol.111.076422 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2012 Mar;81(3):455-64. doi: 10.1124/mol.111.076422. Epub 2011 Dec 
      15.