Figure 6

Chmp1A was translocated to the nucleus in ATRA responsive cells but to the membrane in ATRA resistant cells upon ATRA treatment (A and B), and Model (C). (A) In the presence of DMSO, Chmp1A expression was modestly detected both in the nucleus and cytoplasm in PanC-1 cells (a, c). However, Chmp1A protein expression became robust in the presence of ATRA, especially in the nucleus (n in c, d). (a, b) and (c, d) is one and two days after vehicle or ATRA treatment, respectively. (B) Chmp1A was initially distributed ubiquitously in CRL-2151 cells in the presence of DMSO or ATRA (a, b). From Day 3 on, however, Chmp1A protein was mainly detected and remained at the membrane (arrows in c, d) in both DMSO and ATRA treated cells. (a, b) is for Day 2 and (c, d) is for Day 3 after DMSO and ATRA treatment, respectively. (C) Model: Chmp1A mediates growth inhibition of ATRA signaling. Chmp1A positively regulates the expression of CRBP-1. In turn, CRBP-1 controls the activity of ATRA via regulating the storage and metabolism of retinol A. ATRA treatment produces an increase in the expression level of Chmp1A in the nucleus, which leads to the accumulation of total and 'active' P53 resulting in a decrease in cell proliferation.