TY - JOUR
T1 - Promyelocytic leukemia protein controls cell migration in response to hydrogen peroxide and insulin-like growth factor-1
AU - Reineke, Erin L.
AU - Liu, Yu
AU - Kao, Hung Ying
PY - 2010/3/26
Y1 - 2010/3/26
N2 - Promyelocytic leukemia protein (PML) was originally identified as part of a chromosomal translocation that contributes to the development of acute promyelocytic leukemia (APL). Since its discovery, PML has been found to play diverse roles in different cellular processes. Notably, PML has anti-proliferative and pro-apoptotic activity that supports its role as a tumor suppressor. We have previously shown that the peptidyl-prolyl isomerase Pin1 is able to affect cell proliferation and hydrogen peroxide (H2O 2)-mediated cell death through modulation of the steady-state levels of PML. We have extended these studies to show that the interaction between PML and Pin1 is targeted by multiple extracellular signals in the cell. We show that H2O2 up-regulates and IGF-1 down-regulates PML expression in a Pin1-dependent manner. Interestingly, we found that H2O 2- and IGF-1-mediated alteration in PML accumulation regulate MDA-MB-231 cell migration. Furthermore, we show that the control of cell migration by PML, and thus H2O2 and IGF-1, results from PML-dependent decreased expression of integrin β1 (ITGB1). Knockdown of Pin1 leads to decreased cell migration, lower levels of ITGB1 expression and resistance to IGF-1- and H2O2-induced changes in cell migration and ITGB1 expression. Taken together, our work identifies PML as a common target for H2O2 and IGF-1 and supports a novel tumor suppressive role for PML in controlling cell migration through the expression of ITGB1.
AB - Promyelocytic leukemia protein (PML) was originally identified as part of a chromosomal translocation that contributes to the development of acute promyelocytic leukemia (APL). Since its discovery, PML has been found to play diverse roles in different cellular processes. Notably, PML has anti-proliferative and pro-apoptotic activity that supports its role as a tumor suppressor. We have previously shown that the peptidyl-prolyl isomerase Pin1 is able to affect cell proliferation and hydrogen peroxide (H2O 2)-mediated cell death through modulation of the steady-state levels of PML. We have extended these studies to show that the interaction between PML and Pin1 is targeted by multiple extracellular signals in the cell. We show that H2O2 up-regulates and IGF-1 down-regulates PML expression in a Pin1-dependent manner. Interestingly, we found that H2O 2- and IGF-1-mediated alteration in PML accumulation regulate MDA-MB-231 cell migration. Furthermore, we show that the control of cell migration by PML, and thus H2O2 and IGF-1, results from PML-dependent decreased expression of integrin β1 (ITGB1). Knockdown of Pin1 leads to decreased cell migration, lower levels of ITGB1 expression and resistance to IGF-1- and H2O2-induced changes in cell migration and ITGB1 expression. Taken together, our work identifies PML as a common target for H2O2 and IGF-1 and supports a novel tumor suppressive role for PML in controlling cell migration through the expression of ITGB1.
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U2 - 10.1074/jbc.M109.063362
DO - 10.1074/jbc.M109.063362
M3 - Article
C2 - 20100838
AN - SCOPUS:77951227828
SN - 0021-9258
VL - 285
SP - 9485
EP - 9492
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 13
ER -