3. RB and E2f-2 in terminal red cell differentiation.

Work in the Macleod lab has elucidated a critical role for the RB tumor suppressor in promoting cell cycle exit and maturation of red blood cells. This key function of pRB in terminal erythroid maturation is mediated through its interaction with the E2f-2 transcription factor that is up-regulated during end-stages of red cell differentiation. Current work is focused on understanding the role of pRb in sensing oxidative stress in the erythroid system and its significance for myeloid malignancies.

 

References

Spike, BT, Dirlam, A, Dibling, BC, Marvin, J, Williams, BO, Jacks, T & KF Macleod The Rb tumor suppressor is required for stress erythropoiesis. The EMBO Journal. 23: 4319-29 (2004).

Spike, BT & KF Macleod The Rb tumor suppressor in stress responses and hematopoietic homeostasis. Cell Cycle 4: e181-184 (2005).

Abhinav Diwan, Andrew G Koesters, Amy M Odley, Suvarnamala Pushkaran, Christopher P Baines, Benjamin T Spike, Diedre Daria, Anil G Jegga, Hartmut Geiger, Bruce J Aronow, Jeffrey D Molkentin, Kay F Macleod, Theodosia A Kalfa, Gerald W Dorn II: Unrestrained erythroblast development in Nix-/- mice reveals a mechanism for apoptotic modulation of erythropoiesis. Proc.Natl.Acad.Sci. USA 104, 6794-9 (2007).

Spike, BT, Dibling BC & Macleod, KF: Hypoxic stress underlies defects in erythroblast islands in the Rb null mouse. Blood 110, 2173-81 (2007).

Benjamin T Spike & Kay F. Macleod: Effects of hypoxia on heterotypic macrophage interactions. In press at Cell Cycle 6 (21), (2007).

Dirlam, A. Spike, B.T. & Macleod, KF: De-regulated E2f-2 activity drives deregulated cell cycle and maturation defects in Rb null erythroblasts. In press at Mol.Cell Biol. (2007).