The regulation of E2F by pRB-family proteins

  1. Nicholas Dyson1
  1. Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129 USA

This extract was created in the absence of an abstract.

Much has been written about the functions of the E2F transcription factor and the product of the retinoblastoma tumor suppressor gene (pRB). These proteins have been described in terms that vary from “master regulators of cell cycle and differentiation” to “peripheral factors that lie outside the core cell cycle machinery.” Most often, pRB and E2F are described in short and simple terms as opposing molecules that control the G1- to S-phase transition.

There is an element of truth in each of these descriptions. E2F- and pRB-family proteins clearly play important roles in cell proliferation and differentiation. The extent to which they are master regulators or peripheral factors is a question of semantics, and these terms tell us more about the writer than the proteins. Perhaps the most important development in the E2F literature is the appreciation that E2F and pRB are not unique molecules with functions that can be defined in black and white terms. Instead, E2F and pRB represent families of related proteins that have diverse and occasionally contradictory activities. We now know a great deal about E2F complexes and pRB-family proteins and the emerging picture defies a one-line explanation. The fascinating variety of activities ascribed to various E2F complexes challenges us to place these into context and to find the right perspective.

This review is presented into two sections. The first section summarizes the tremendous progress into the composition and properties of E2F and the many interactions that coordinately regulate E2F-dependent transcription. The rapid growth in the size of the E2F literature hides the fact that several fundamental questions have not been fully answered. Because of this, the second section of this review details five unresolved issues that have been highlighted by recent publications. It is impossible to cover all of the relevant E2F literature in …

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