Abstract:
:Zbed3, a BED finger domain-containing protein was found to promote cancer proliferation by regulating β-catenin expression through interacting with Axin. But whether and how BED finger domain function in regulating cancer proliferation is unknown. We constructed five mutants of Zbed3, which lacks the Axin-Zbed3 binding site, and the 43 to 52, 69 to 77, 87 to 92, and 97 to 104 sequences in BED finger domain, respectively and named them as Z-A, Z1, Z2, Z3, and Z4. Transfection of both wild-type of Zbed3 and the mutants Z1, Z3, and Z4 (P < 0.05), but not Z2 (P > 0.05) significantly upregulated β-catenin expression in NCI-H1299 cells. Overexpression of both wild-type of Zbed3 and the mutants Z1, Z3, and Z4 (P < 0.05) but not Z2 (P > 0.05) significantly promoted cancer cell proliferation and invasion. The ability of proliferation (P < 0.05) but not invasion (P < 0.05) of cancer cells transfected with Z1 and Z4 was significantly lower than that with wild-type Zbed3 and Z3. Overexpression of wild-type Zbed3 (P < 0.05) but not the mutant Z-A, which lacks the binding site with Axin and Z2 (P > 0.05) significantly upregulated the interaction of Axin and Zbed3, β-catenin expression and the activity of Wnt signaling. Both overexpression of wild-type Zbed3 and the mutant Z1 and Z4 significantly upregulated the activity of Wnt signaling and promoted cancer cell proliferation (P < 0.05) but only overexpression of wild-type Zbed3 (P < 0.05), but not the mutant Z1, and Z4 (P > 0.05), significantly upregulated the expression of proliferating cell nuclear antigen (PCNA) in NCI-H1299 cells. These results indicate that Zbed3 may promote lung cancer cell proliferation through regulating PCNA expression besides regulating β-catenin expression and BED finger domain can impact on this function.
journal_name
J Cell Biochemjournal_title
Journal of cellular biochemistryauthors
Liu H,Shi X,Fan X,Zhang D,Jiang B,Zhao Y,Fan Cdoi
10.1002/jcb.28498subject
Has Abstractpub_date
2019-08-01 00:00:00pages
12340-12347issue
8eissn
0730-2312issn
1097-4644journal_volume
120pub_type
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