Analysis of pRb Family Binding Regions of Adenovirus Type 12 E1A

概要

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Adenovirus early 1A (E1A) products can form complexes with cellular pro-teins including the pRb tumor suppressor, pRb-related p107 and p130, and p300 proteins related to the CREB-binding protein (CBP) . Within the E1A sequence, CR2 and CR1 mediate interaction with pRb family proteins, and the amino termi-nus and CR1 are involved in association with p300 protein. These interactions are essential for the transforming activity of ElA proteins of various adenovirus serotypes. Since E1A of highly oncogenic adenovirus type 12 (Ad12) have some differences in transformation efficiency and oncogenicity from non-oncogenic Ad5 E1A, we have analyzed the role of CR1 and CR2 sequences of Ad12 E1A in trans-formation and pRb family binding using specific mutations. On the basis of the characteristic phenotypes of some CR1 mutations we suggest a modification of the previously proposed consensus regarding CR1 sequence for pRb binding. Combinations of CR1 and CR2 mutations revealed different roles for noncon-served residues within the conserved pRb binding motif LXCXE of CR2, and interaction of CR1 and CR2 of Ad12 E1A through specific amino acid residue is suggested. These structural features of Ad12 E1A proteins may explain at least in part the functional differences from Ad5 E1A proteins.
札幌医科大学の論文
1996-00-00