PMID- 28194465
OWN - NLM
STAT- MEDLINE
DCOM- 20171121
LR  - 20180713
IS  - 1756-591X (Electronic)
IS  - 1756-5901 (Linking)
VI  - 9
IP  - 3
DP  - 2017 Mar 22
TI  - Unravelling the role of protein kinase CK2 in metal toxicity using gene deletion 
      mutants.
PG  - 301-308
LID - 10.1039/c6mt00230g [doi]
AB  - Metal ions, biologically essential or toxic, are present in the surrounding 
      environment of living organisms. Understanding their uptake, homeostasis or 
      detoxification is critical in cell biology and human health. In this study, we 
      investigated the role of protein kinase CK2 in metal toxicity using gene deletion 
      strains of Saccharomyces cerevisiae against a panel of six metal ions. The 
      deletion of CKA2, the yeast orthologue of mammalian CK2alpha', leads to a pronounced 
      resistant phenotype against Zn(2+) and Al(3+), whilst the deletion of CKB1 or 
      CKB2 results in tolerance to Cr(6+) and As(3+). The individual deletion mutants 
      of CK2 subunits (CKA1, CKA2, CKB1 and CKB2) did not have any benefit against 
      Co(2+) and Cd(2+). The metal ion content in the treated cells was then measured 
      by inductively coupled plasma mass spectrometry. Two contrasting findings were 
      obtained for the CKA2 deletion mutant (cka2Delta) against Al(3+) or Zn(2+). Upon 
      exposure to Al(3+), cka2Delta had markedly lower Al(3+) content than the wild type 
      and other CK2 mutants, congruous to the resistant phenotype of cka2Delta against 
      Al(3+), indicating that CKA2 is responsible for Al(3+) uptake. Upon zinc exposure 
      the same mutant showed similar Zn(2+) content to the wild type and cka1Delta. 
      Strikingly, the selective inhibitor of CK2 TBB 
      (4,5,6,7-tetrabromo-1H-benzotriazole) abolished the resistant phenotype of cka2Delta 
      against Zn(2+). Hence, the CK2 subunit CKA1 plays a key role in Zn(2+) 
      sequestration of the cell. Given that both zinc and CK2 are implicated in cancer 
      development, the findings herein are of significance to cancer research and 
      anticancer drug development.
FAU - Johnson, Adam J
AU  - Johnson AJ
AD  - School of Science and Health, Western Sydney University, Locked Bag 1797, 
      Penrith, NSW 2751, Australia. m.wu@westernsydney.edu.au.
FAU - Zaman, Mohammad S
AU  - Zaman MS
AD  - School of Science and Health, Western Sydney University, Locked Bag 1797, 
      Penrith, NSW 2751, Australia. m.wu@westernsydney.edu.au.
FAU - Veljanoski, Filip
AU  - Veljanoski F
AD  - School of Science and Health, Western Sydney University, Locked Bag 1797, 
      Penrith, NSW 2751, Australia. m.wu@westernsydney.edu.au.
FAU - Phrakaysone, Alex A
AU  - Phrakaysone AA
AD  - School of Science and Health, Western Sydney University, Locked Bag 1797, 
      Penrith, NSW 2751, Australia. m.wu@westernsydney.edu.au.
FAU - Li, Suhua
AU  - Li S
AD  - College of Life Sciences, Southwest Forestry University, 300 Bailong Road, 
      Kunming 650024, Yunnan Province, P. R. China.
FAU - O'Doherty, Patrick J
AU  - O'Doherty PJ
AD  - School of Science and Health, Western Sydney University, Locked Bag 1797, 
      Penrith, NSW 2751, Australia. m.wu@westernsydney.edu.au.
FAU - Petersingham, Gayani
AU  - Petersingham G
AD  - School of Science and Health, Western Sydney University, Locked Bag 1797, 
      Penrith, NSW 2751, Australia. m.wu@westernsydney.edu.au.
FAU - Perrone, Gabriel G
AU  - Perrone GG
AD  - School of Science and Health, Western Sydney University, Locked Bag 1797, 
      Penrith, NSW 2751, Australia. m.wu@westernsydney.edu.au.
FAU - Molloy, Mark P
AU  - Molloy MP
AD  - Australian Proteome Analysis Facility (APAF), Dept. Chemistry and Biomolecular 
      Sciences, Macquarie University, Sydney, NSW 2109, Australia.
FAU - Wu, Ming J
AU  - Wu MJ
AUID- ORCID: 0000-0003-0577-1907
AD  - School of Science and Health, Western Sydney University, Locked Bag 1797, 
      Penrith, NSW 2751, Australia. m.wu@westernsydney.edu.au and Molecular Medicine 
      Research Group, School of Medicine, Western Sydney University, Locked Bag 1797, 
      Penrith, NSW 2751, Australia.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Metallomics
JT  - Metallomics : integrated biometal science
JID - 101478346
RN  - 0 (Metals)
RN  - EC 2.7.11.1 (Casein Kinase II)
SB  - IM
MH  - Casein Kinase II/*genetics
MH  - *Gene Deletion
MH  - Heavy Metal Poisoning/enzymology/*etiology
MH  - Metals/*toxicity
MH  - Saccharomyces cerevisiae/*drug effects/enzymology/genetics
EDAT- 2017/02/15 06:00
MHDA- 2017/11/29 06:00
CRDT- 2017/02/15 06:00
PHST- 2017/02/15 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2017/02/15 06:00 [entrez]
AID - 10.1039/c6mt00230g [doi]
PST - ppublish
SO  - Metallomics. 2017 Mar 22;9(3):301-308. doi: 10.1039/c6mt00230g.