The RASSF proteins in cancer; from epigenetic silencing to functional characterization.
The Ras-Association Domain Family (RASSF) comprises ten members, termed RASSF1 to RASSF10. RASSF1 to RASSF6 harbor a C-terminal Ras-association (RA) domain and RASSF7 to RASSF10 contain an N-terminal RA domain. Interestingly, it was observed that in various tumor types distinct RASSFs transcripts (e.g. RASSF1A and RASSF2A) are missing due to hypermethylation of their CpG island promoter. Since methylation of the RASSF1A promoter is described as an early and frequent event in tumorigenesis, RASSF1A could serve as a useful diagnostic marker in cancer screens. RASSFs are implicated in various cellular mechanisms including apoptosis, cell cycle control and microtubule stabilization, though little is known about the underlying mechanisms. Tumor suppressing functions were reported for several members. Here we review the current literature on RASSF members focusing on structural, functional and epigenetic aspects. Characterizing the cellular mechanisms that regulate the signaling pathways RASSFs are involved in, could lead to a deeper understanding of tumor development and, furthermore, to new strategies in cancer treatment.
Institute for Genetics, Justus Liebig University Giessen, Heinrich-Buff-Ring 58-62, D-35392 Giessen, Germany.
Antje M
AM
Richter
Gerd P
GP
Pfeifer
Reinhard H
RH
Dammann
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002453:Cell Cycle; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D011905:Genes, ras; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C411762:RASSF1 protein, human; C425300:RASSF2 protein, human; C454041:RASSF3 protein, human; C495500:RASSF4 protein, human; C454042:RASSF5 protein, human; D025521:Tumor Suppressor Proteins; D020559:Monomeric GTP-Binding Proteins