The FASEB Journal, Vol 7, 841-845, Copyright © 1993 by The Federation of American Societies for Experimental Biology

REVIEWS

The retinoblastoma gene: role in cell cycle control and cell differentiation

KG Wiman
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.

The retinoblastoma (RB) gene is the prototype tumor suppressor gene. It encodes a nuclear protein that acts as a cell cycle control checkpoint at the G1 phase. Deletion or inactivation of both RB alleles plays an essential, rate-limiting role in retinoblastoma and in the osteosarcomas that arise within families that carry a mutated RB gene. RB inactivation is also found in other sarcomas, small cell carcinoma of the lung, and in carcinoma of the breast, bladder, and prostate. Transforming proteins encoded by SV40, and the transforming or tumor- associated subtypes of adenoviruses and human papilloma viruses (HPV) can bind RB, thereby blocking its normal function. The EBNA-5 protein of Epstein-Barr virus (EBV) is also able to bind RB in vitro. In addition, RB can interact with several cellular proteins, including the transcription factor E2F. RB gene knock-out mice die in utero around day 14 of gestation. The embryos show disturbed neural and hematopoietic differentiation, indicating that RB is vitally important for these processes. This notion is further supported by studies demonstrating that RB expression in mouse embryo tissues is highest in cells undergoing differentiation, and that RB is required for MyoD- induced muscle differentiation.

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