MOLECULAR-CLONING, CHROMOSOMAL MAPPING, AND EXPRESSION OF THE MOUSE P107 GENE

Progression through the G1 phase of the cell cycle is regulated, in pa rt, by the pRB-family proteins, pRB and p107. The basis for this regul ation is due to a network of interactions between the pRB-family prote ins, pRB, p107, and p130; the E2F-family of transcription factors; and cyclins D, E, and A. One of the pRB-family proteins, p107, has also b een found to bind to the transactivation domain of the c-Myc proto-onc ogene. This region in c-Myc is frequently mutated in tumors such as Bu rkitt's lymphoma, HIV-associated lymphoma, and multiple myeloma. The b inding of p107 and regulation of c-Myc may conceivably be disrupted no t only by mutations in c-Myc, but possibly by mutations in p107. In or der to determine if mutations in p107 are indeed present in mouse B-ce ll tumors which exhibit a lower frequency of c-Myc mutation, we have c loned the mouse p107 cDNA and compared this sequence with its human co unterpart. We find that the extreme N-terminal and C-terminal regions are the most conserved between human and mouse p107 sequences. Chromos omal positioning of the locus for p107 (designated Rbl1) as well as E2 f1 to the distal end of mouse Chromosome (Chr) 2 also suggests a close but unlinked genetic relationship between these cell cycle regulatory transcription factors.