Send to

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 2007 Jul 27;282(30):21962-72. Epub 2007 Jun 1.

Survival factor withdrawal-induced apoptosis of TF-1 cells involves a TRB2-Mcl-1 axis-dependent pathway.

Author information

Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan.


Tribbles, an atypical protein kinase superfamily member, coordinates cell proliferation, migration, and morphogenesis during the development of Drosophila and Xenopus embryos. Although Tribbles are highly conserved throughout evolution, the physiological functions of mammalian Tribbles family remain largely unclear. Here we report that human TRB2 is a pro-apoptotic molecule that induces apoptosis of cells mainly of the hematopoietic origin. TRB2 mRNA is selectively induced by removal of granulocyte macrophage colony-stimulating factor (GM-CSF) or interleukin-2 from human erythroleukemia-derived TF-1 cell line or activated primary CD4(+) T cells, respectively. It is, however, not induced by many other treatments that trigger apoptosis of these two cell types. Overexpression of TRB2 activates many apoptotic events observed in GM-CSF-deprived TF-1 cells, including loss of mitochondrial membrane potential, Mcl-1 cleavage/degradation, and activation of Bax and a number of caspases. Specific knockdown of TRB2 significantly suppresses GM-CSF deprivation-induced apoptosis and all apoptotic events mentioned above. Finally, we demonstrate that TRB2-induced cleavage and degradation of Mcl-1 are mediated via a caspase-dependent but proteasome-independent mechanism, and overexpression of Mcl-1 or its upstream activator Akt can markedly overcome the apoptogenic effect of TRB2. Altogether, these results suggest that the TRB2-Mcl-1 axis plays an important role in survival factor withdrawal-induced apoptosis of TF-1 cells.

[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center