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STIP Regulates ERK1/2 Signaling Pathway Involved in Interaction with PP1γ in Lymphoblastic Leukemia

[ Vol. 16 , Issue. 8 ]

Author(s):

S. Sun, Y. Wang, H. Chen, L. Fang, Y. Cui, X. Han, D. Wu, H. Li, M. Ye, X. Zhao and J. Liu   Pages 767 - 775 ( 9 )

Abstract:


Background: Sip1/Tuftelin Interacting Protein (STIP) is highly conserved from Caenorhabditis elegans to Homo sapiens and has essential biological functions. However, its function in leukemia remains unknown.

Methods: Clinic samples and cell model were used in this article to investigate the expression of STIP in lymphoblastic leukemia. The functional research of STIP was performed in ARH-77 by siRNA transfection, immunofluorescence, cell count, cell cycle analysis, qRT-PCR, sub-cellular fractionation assays, immunoprecipitation and western blotting.

Results: Here, we found that STIP is more highly expressed in both clinical lymphoblastic leukemia samples and cultured leukemia cells than in normal samples. Knockdown of STIP in B lymphoblastic leukemia ARH-77 cells leads to S phase arrest, lower cell proliferation rates, and suppressed AKT and ERK1/2 signaling pathways. Interestingly, when protein phosphatase was inhibited by Calyculin A, STIP knockdown did not result in the dephosphorylation of p-ERK1/2, suggesting the dependence of STIP on protein phosphatase in the regulation of ERK1/2. Among those protein phosphatase inhibited by Calyculin A, PP1γ was found to interact with STIP proven by immunofluorescence and immunoprecipitation assays. The binding of STIP with PP1γ may decrease the phosphatase activity of PP1γ, resulting in hyper-activated ERK1/2 signaling.

Conclusion: In summary, the high expression and activation effect on the ERK1/2 signaling of STIP in lymphoblastic leukemia suggest that STIP would be a potential therapy target or diagnosis marker for leukemia.

Keywords:

STIP, lymphoblastic leukemia, ERK1/2, PP1γ.

Affiliation:

Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, China., State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha 410008, China.



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