The Schizosaccharomyces pombe cdc5 gene product is a cell cycle regulator that exerts its effects at the G2/M transition in fission yeast. We describe the cloning of a putative human transcription factor, pombe Cdc5-related protein (PCDC5RP), which bears significant homology to S. pombe Cdc5 and to expressed sequences in mouse, nematode, and budding yeast. PCDC5RP is expressed widely in normal adult human tissues and thus may have an important general function that has been preserved evolutionarily. PCDC5RP contains two tandem repeats of a helix-turn-helix DNA binding motif, four consensus nuclear localization signals, and a hydrophilic, proline-rich central region similar to the transcriptional activating domain in Myb family members. Remarkably, PCDC5RP moved rapidly from cytoplasm to nucleus upon serum stimulation of cultured cells. This movement correlated temporally with an increase in PCDC5RP phosphorylation. Thus, PCDC5RP is a presumed transcription factor that appears to transduce cytoplasmic signals to the nucleus upon serum stimulation.