Serine-Threonine Kinase, activated by GTP-Ras, Raf phosphorylates MEK-1.

The retinoblastoma (Rb) gene was the first tumor suppressor gene to be identified and was isolated by positional cloning from retinoblastoma tumors (Lee et al., 1987, Science, 235: 1394-99). Rb is a phosphoprotein that arrests cells during the G1 phase of the cell cycle by repressing transcription of genes required for the G1-S-transition. A major target of Rb is the E2F family of transcription factors (E2F) to which Rb binds in its hypo-phosphorylated state. Progression of a cell through G1 and S phase requires inactivation of Rb by its phosphorylation by cyclin-dependent kinases complexed to their cyclin partners such as Cdk4-CyclinD or Cdk6-CyclinD or Cdk2-CyclinE. Loss of Rb function triggers the p53 apoptotic pathway, which may serve as an intrinsic protective mechanism for eliminating cells in which the Rb is deregulated. Loss of Rb presumably imposes pressure on tumor cells to also inactivate the p53-dependent apoptotic pathway in order to survive. A link between Rb and p53 is provided by the E2F transcriptional target ARF (Harbour and Dean, 2000, Nat. Cell Biol., 2: E65-67).

Reaper is one of three pro-apoptotic genes identified in the Drosophila H99 gene region (Reaper region). It encodes a 65 aa cytoplasmic protein which, upon overexpression, promotes potent apoptotic activity in vivo and in vitro. Up to now, Reaper-like proteins have not been discovered in other organisms, but interestingly, Reaper is able to induce apoptotic activity in Xenopus, murine, and human systems, indicating a conserved function(s). Like hid and Grim, Reaper contains the N-terminal 14-amino-acid RHG motif, which (in the case of Reaper) is sufficient but not necessary for killing. The mechanism by which Reaper mediates cell-death is not known, yet, but appears to involve caspase-activation and interaction with IAPs. (reviewed by Abrams JM, Trends Cell Biol.,1999, 9: 435-440).

Reaper region
The Reaper region is a complex locus in the Drosophila genome to which cell-death defective phenotypes have been mapped. The Reaper region is located within the H99 deletion region and contains the pro-apoptotic Drosophila genes Reaper, Grim and Hid (reviewed by Abrams JM, 1999, Trends Cell Biol., 9: 435-440).

Rel proteins
Family of structurally Related proteins which are the subunits of the NF-kB transcription factor. Five different Rel proteins (also called Rel/NF-kB proteins) have been identified so far: p50, p52, p65, Rel-B, and cRel. All those Rel proteins contain a conserved N-terminal region, called the Rel Homology Domain (RHD). More....

RHG motif
The RHG motif is a 14-amino-acid sequence common to the Drosophila cell-death genes Reaper, Hid and Grim. It is located at their N-terminus and is presumably involved in the interaction with IAPs. The RHG domain is sufficient to mediate a killing effect but is not necessary for the killing of Reaper and Grim.

Rel Homology Domain (RHD), the conserved N-terminal domain of Rel/NF-kB proteins. It contains the DNA-binding and dimerization domains and the nuclear localization signal.More....

The human reovirus is a double-stranded RNA virus. Since reovirus infections are in general asymptomatic and reovirus replication depends on an activated Ras signalling pathway it may be useful in tumor therapy since many tumors display increased ras activity. Indeed, reovirus was shown to selectively infect ras overexpressing tumor cells and suppress tumor growth (Coffey et al., 1998, Science, 282: 1332).

RGD tripeptide
Arginine-glycine-aspartate tripeptide motif which can be found in proteins of the extracellular matrix. Integrins link the intracellular cytoskeleton of cells with the extracellular matrix by recognizing this RGD motif. Without attachment to the extracellular matrix, cells normally undergo apoptosis ('anoikis'). Soluble RGD peptides induce apoptosis and might be used as drugs against angiogenesis, inflammation and cancer mestastasis. More.

RING finger
Really Interesting New Gene (RING) fingers display a series of histidine and cysteine residues with a characteristic spacing that allows the coordination of two zinc ions. RING finger domains are found in many proteins and have been implicated in various cellular functions. RINGs presumably do not function as chemical catalysts but as molecular scaffolds that bring together other proteins such as E3 ubiquitin ligases with E2 ubiquitin conjugating enzymes and the corresponding substrate.

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