Role of LXCXE motif-dependent interactions in the activity of the retinoblastoma protein

Chan, H.M., Smith, L. and La Thangue, N.B. (2001) Role of LXCXE motif-dependent interactions in the activity of the retinoblastoma protein. Oncogene, 20, pp. 6152-6163.

Abstract

Cell cycle control by pRb requires the integrity of the pocket domain, which is a region necessary for interactions with a variety of proteins, including E2F and LXCXE-motif containing proteins. Through knowledge of the crystal structure of pRb we have prepared a panel of pRb mutant derivatives in which a cluster of lysine residues that demark the LXCXE peptide binding domain were systematically mutated. One of the mutant derivatives, Rb6A, exhibits significantly reduced LXCXE-dependent interactions with HPV E7, cyclinD1 and HDAC2, but retained LXCXE-independent binding to E2F. Consistent with these results, Rb6A could down-regulate E2F-1-dependent activation of different E2F responsive promoters, but was compromised in Rb-dependent repression. Most importantly, Rb6A retained wild-type growth arrest activity, and colony forming activity similar to wild-type pRb. It is compatible with these results that directly targeting HDAC2 to E2F responsive promoters as an E2F/HDAC hybrid protein failed to effect cell cycle arrest. These results suggest that LXCXE-dependent interactions are not essential for pRb to exert growth arrest.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Smith, Mrs Linda
• Authors: Chan, H.M., Smith, L., and La Thangue, N.B.
• Subjects: Q Science > QR Microbiology
• College/School: College of Medical Veterinary and Life Sciences
• Journal Name: Oncogene
• ISSN: 0950-9232