IDENTIFICATION OF A LARGE MYC-BINDING PROTEIN THAT CONTAINS RCC1-LIKEREPEATS

The protooncogene MYC plays an important role in the regulation of cel lular proliferation, differentiation, and apoptosis and has been impli cated in a variety of human tumors. MYC and the closely related MYCN e ncode highly conserved nuclear phosphoproteins (Myc and NMyc) that app arently function as transcription factors in the cell, We have identif ied a large and highly conserved nuclear protein that interacts direct ly with the transcriptional activating domain of Myc (designated ''pro tein associated with Mgc'' or Pam). Pam contains an extended amino aci d sequence with similarities to a protein known as regulator of chromo some condensation (RCC1), which mag play a role in the function of chr omatin, The gene encoding Pam (PAM) is expressed in all of the human t issue examined, but expression is exceptionally abundant in brain and thymus, Pam binds specifically to Myc, but not NMyc. The region in MSc required for binding to Pam includes a domain that is essential for t he function of Myc and that is frequently mutated in Burkitt's lymphom as. PAM is located within a 300-kb region on chromosome 13q22.