Porphobilinogen deaminase (PBGD) is a rate-limiting
enzyme of the
heme biosynthesis pathway, whose level is elevated in various human
tumors. PBGD was observed in both nuclear and cytoplasmic fractions of C6
glioma cells by immunostaining. During mitosis, chromatids were intensely stained for PBGD in comparison to the interphase
chromatin. Using the yeast two-hybrid system, we identified
RanBPM, the nuclear Ran-
binding protein, as an interacting partner of PBGD. During
butyrate-induced differentiation of C6, both nuclear and cytoplasmic PBGD levels declined as did
Ran protein and its
nucleotide exchange factor RCC1. N,N'-hexamethylene bis-
acetamide-dependent differentiation resulted in an increase of the cytoplasmic PBGD, whereas nuclear PBGD,
Ran protein and RCC1 remained unchanged.
mRNA levels of PBGD remained unchanged during stimulation with both
butyrate and N,N'-hexamethylene bis-
acetamide. The enzymatic activity of PBGD and
protoporphyrin IX synthesis in C6 cells were dependent on the differentiation induction agent. We conclude that PBGD possibly has a nuclear role in addition to its cytosolic enzymatic activity required for
heme synthesis, which is related to cell transformation and differentiation.