Specificity of E2F1, E2F2, and E2F3 in mediating phenotypes induced by loss of Rb. Cell Growth Differ 2002 May;13(5):215-25
Date
06/18/2002Pubmed ID
12065245Scopus ID
2-s2.0-0035997933 (requires institutional sign-in at Scopus site) 93 CitationsAbstract
The Rb/E2F pathway plays a critical role in the control ofcellular proliferation. Here, we report that E2F1, E2F2, and E2F3 make major individual contributions toward the in vivo phenotypic consequences of Rb deficiency. In the developing lens of Rb(-/-) embryos, loss of E2F1, E2F2, or E2F3 reduces the unscheduled proliferation of fiber cells, with the loss of E2F3 having the most pronounced effect. In Rb-deficient retinas, all three E2Fs contribute equally to the ectopic proliferation of postmitotic neuronal cells. In contrast, E2F1 is unique in mediating apoptosis in both Rb(-/-) lenses and retinas. In the central nervous system, loss of E2F1 or E2F3 can almost completely eliminate the ectopic DNA replication and apoptosis observed in Rb(-/-) embryos, and loss of E2F2 partially reduces the unscheduled DNA replication and has no effect on apoptosis. These results provide clear evidence for functional specificity among E2Fs in the control of Rb-dependent proliferation and apoptosis in a tissue-specific manner.
Author List
Saavedra HI, Wu L, de Bruin A, Timmers C, Rosol TJ, Weinstein M, Robinson ML, Leone GAuthor
Gustavo Leone PhD Sr Associate Dean, Director, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Cell Cycle Proteins
Cell Division
DNA-Binding Proteins
E2F Transcription Factors
E2F1 Transcription Factor
E2F2 Transcription Factor
E2F3 Transcription Factor
Female
Fetal Death
Gene Expression Regulation, Developmental
Mice
Mice, Knockout
Phenotype
Pregnancy
Retina
Retinoblastoma Protein
Transcription Factors