Figure 112

Proposed mechanism of action for rapamycin (rapa). Rapamycin binds to FK-binding protein (FK-BP). However, the immunosup-pressive properties of rapamycin are not due to inhibition of cal-cineurin. Rapamycin blocks the activating signal delivered by growth factors (exemplified by the interleukin-2 [IL-2] receptor) by blocking the translation of the coding of messenger RNA (mRNA) for key proteins required for progression through the G1 phase of the cell cycle. In this model the mammalian target of rapamycin (m-TOR, also called FRAP or RAFT1), phosphorylates the translational repressor PHAS-I. Arrest of the cell cycle results, and the proliferation of lymphocytes is thereby inhibited. The full understanding of the mechanism(s) of action of rapamycin is the focus of intense research at this time [2]. elF-4—translation initiation factor belonging to the Ets family; G(0 1 and 2)—quiescent; M—mitosis; S—synthesis.

PRPP + Adenine

PRPP + Adenine

Mycophenolate, mizoribine

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