We performed a yeast interactive screen in search of p19(ARF)-binding partners and have isolated a novel serine rich protein that is assigned to human chromosome 4q35 and mouse chromosome 8. The human and mouse proteins showed 84.2% homology. It is named CARF for its role as a putative Collaborator of ARF. CARF binds to both mouse and human ARF proteins. Its expression was detected in a variety of human tissues. The cDNA was expressed in bacteria and mammalian cells as a soluble and predominantly nucleoplasmic protein, respectively. CARF is a novel binding partner of ARF and might be involved in its p53-dependent or -independent tumor suppressive functions.