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1579240 
Journal Article 
p27 Suppresses cyclooxygenase-2 expression by inhibiting p38β and p38δ-mediated CREB phosphorylation upon arsenite exposure 
Che, X; Liu, J; Huang, H; Mi, X; Xia, Q; Li, J; Zhang, D; Ke, Q; Gao, J; Huang, C 
In Press 
Biochimica et Biophysica Acta
ISSN: 0006-3002
EISSN: 1878-2434 
1833 
2083-2091 
English 
p27 is a cyclin-dependent kinase (CDK) inhibitor that suppresses a cell's transition from G0 to S phase, therefore acting as a tumor suppressor. Our most recent studies demonstrate that upon arsenite exposure, p27 suppresses Hsp27 and Hsp70 expressions through the JNK2/c-Jun- and HSF-1-dependent pathways, suggesting a novel molecular mechanism underlying the tumor suppressive function of p27 in a CDK-independent manner. We found that p27-deficiency (p27-/-) resulted in the elevation of cyclooxygenase-2 (COX-2) expression at transcriptional level, whereas the introduction of p27 brought back COX-2 expression to a level similar to that of p27+/+ cells, suggesting that p27 exhibits an inhibitory effect on COX-2 expression. Further studies identified that p27 inhibition of COX-2 expression was specifically due to phosphorylation of transcription factor cAMP response element binding (CREB) phosphorylation mediated by p38β and p38δ. These results demonstrate a novel mechanism underlying tumor suppression effect of p27 and will contribute to understanding of the overall mechanism of p27 tumor suppression in a CDK-independent manner. 
p27; COX-2; p38; CREB; Arsenite 
IRIS
• Arsenic Hazard ID
          PubMed
          Considered New
          WOS
          Considered New
          PubMed
          Considered New
          PubMed
          ToxNet
          Considered New
          WOS
          ToxNet
          Excluded
               Toxnet Duplicates
          ToxNet
          Excluded
               Toxnet Duplicates
          ToxNet
          Excluded
               Toxnet Duplicates
     2. Lit Search Updates through Oct 2015
          PubMed
          WOS
          ToxNet
          Considered
     7. Other Studies through Oct 2015
          MOA
• Arsenic (Inorganic)
     1. Literature
          Lit search updates through Oct 2015
     3. Hazard ID Screening
          Other potentially supporting studies
     4. Adverse Outcome Pathways/Networks Screening
          Relevant
• Arsenic MOA
     4. Adverse Outcome Pathways
          Other MOA
     1. MOA Literature Screening
          Health Effect Screening