PLCɛ and the RASSF family in tumour suppression and other functions

Abstract

Not all proteins implicated in direct binding to Ras appear to have a positive role in the generation and progression of tumours; examples include Phospholipase C epsilon (PLCɛ) and some members of the Ras-association domain family (RASSF). The RASSF family comprises of ten members, known as RASSF1 to RASSF10. PLCɛ and RASSF members carry a common Ras-association domain (RA) that can potentially bind Ras oncoproteins and mediate Ras-regulated functions. RASSF1 to RASSF6 also share a common SARAH domain that facilitates protein-protein interactions with other SARAH domain proteins. The majority of the family are frequently downregulated by epigenetic silencing in cancers. They are implicated in various important biological processes including apoptosis, microtubule stabilisation and cell cycle regulation. Recent studies have reinforced the tumour suppressive properties of the RASSF family, with new evidence of emerging pathways and novel functions that suggest a wider role for these proteins. This review will first describe an emerging role of PLCɛ in tumour suppression and then focus on and summarise the new findings on the RASSF family in the last five years to consolidate their well-established functions, and highlight the new regulatory roles of specific RASSF members.