Abstract
Pokemon is an important proto-oncogene involved in various biological processes and cancer development, such as cell differentiation, tumorigenesis and metastasis. Pokemon is recognized as a transcription factor localized upstream of several oncogenes, regulating their expression. p38MAPKs act as key regulatory factors in cellular signaling pathways associated with inflammatory responses, cell proliferation, differentiation and survival. p38β, a member of p38MAPK family, is closely correlated with tumorigenesis, but the mechanism of activation remains unclear. In this study, we found overexpression of Pokemon promoted the growth, migration and invasion of HepG2 cells. However, a p38 inhibitor SB202190 efficiently attenuated the promoting effect of Pokemon in the HepG2 cells. Targeted expression or silencing of Pokemon changed cellular p38β protein level and phosphorylation of downstream ATF2 in the p38 signaling pathway. Both dual luciferase report assay and ChIP assay suggested that p38β is a novel regulatory target of the transcription factor Pokemon and positively regulated by Pokemon in hepatic cells.
Highlights
Pokemon (POK erythroid myeloid ontogenic factor), named as Zbtb7A, LRF, FBI-1 and OCZF, contains an N-terminal POZ/BTB domain mediating protein-protein interaction and aC-terminal Krüppel zinc finger domain responsible for DNA binding [1]
We examined Pokemon expression in several hepatic cell lines and found the expression level of Pokemon is correlated with the malignancy of hepatic cells (Figure 1)
Our results showed that ectopic expression of Pokemon significantly promoted HepG2 proliferation (Figure 2a(i)); Pokemon silencing did not notably affect HepG2 cell proliferation (Figure 2a(ii))
Summary
Pokemon (POK erythroid myeloid ontogenic factor), named as Zbtb7A, LRF, FBI-1 and OCZF, contains an N-terminal POZ/BTB domain mediating protein-protein interaction and aC-terminal Krüppel zinc finger domain responsible for DNA binding [1]. Pokemon (POK erythroid myeloid ontogenic factor), named as Zbtb7A, LRF, FBI-1 and OCZF, contains an N-terminal POZ/BTB domain mediating protein-protein interaction and a. Pokemon is an important transcriptional factor with multiple biological functions, which was originally identified by binding to the inducer of short transcripts (IST) element of human wild type HIV-1 [1]. Pokemon interacts with POZ family members to form a homo- or hetero-dimer participating in various biological processes through its POZ/BTB domain [4]. Pokemon acts as a transactive or suppressive transcription factor [12,13], inhibiting p53 (mediated through the ARF-Mdm2-p53 pathway) [5] and Rb gene transcription [14] but promoting NF-κB transcription and nuclear localization [15,16]. Pokemon plays a pivotal role in tumorigenesis as a proto-oncogene localized upstream of several oncogenes [17]
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