(A) Schematic of human KLF4 with previously identified domains as well as deletion mutants used in the present study. AD, activation domain. RD, repression domain. NLS, nuclear localization signal. DBD, DNA-binding domain. (B) Deletion of KLF4 amino acids 1–108 stabilizes KLF4. Vectors for FLAG-HA-tagged wild type (wt) or deletion mutants of KLF4 were transfected into U2OS. 2 days after transfection cells were mock or cycloheximide (CHX) treated for 6 hours. Equal protein amounts of whole cell lysates were probed for KLF4 mutant levels by immunoblot with an antibody against the hemagglutinin (HA) tag. (C) Fine mapping of the amino-terminal KLF4 region required for degradation. The indicated deletion mutants were tested like in B. (D, E) An amino-terminal region of KLF4 is required for its interaction with KLF4. Beads with GST alone or GST-fused pVHL were incubated with various in vitro translated deletion mutants of KLF4 and bound proteins were analyzed by SDS-PAGE plus autoradiography. Deletion of amino acids 41–50 that stabilize KLF4 (C) does not affect pVHL binding (E).