Abstract
The RASSF family of proteins has been extensively studied in terms of their genetics, structure and function. One of the functions that has been increasingly studied is the role of the RASSF proteins in the DNA damage response. Surprisingly, this research, which encompasses both the classical and N-terminal RASSF proteins, has revealed an involvement of the RASSFs in oncogenic pathways as well as the more familiar tumour suppressor pathways usually associated with the RASSF family members. The most studied protein with respect to DNA damage is RASSF1A, which has been shown, not only to be activated by ATM, a major regulator of the DNA damage response, but also to bind to and activate a number of different pathways which all lead to and feedback from the guardian of the genome, p53. In this review we discuss the latest research linking the RASSF proteins to DNA damage signalling and maintenance of genomic integrity and look at how this knowledge is being utilised in the clinic to enhance the effectiveness of traditional cancer therapies such as radiotherapy.
Highlights
RASSF proteins were originally designated on the basis of sequence homology to domains that associate with Ras-like small GTP-binding proteins
These domains are known as Ras association (RA) domains [RalGDS (Ral guanine nucleotide dissociation stimulator)/AF6 (ALL-1 fusion partner from chromosome 6)] and are distinct from Ras-binding domains (RBD) which bind an alternative set of Ras effectors [1, 2]
Ras-association domain containing family members are important tumour suppressors involved in linking cellular stresses to cell cycle arrest and apoptosis (Figure 2)
Summary
RASSF proteins were originally designated on the basis of sequence homology to domains that associate with Ras-like small GTP-binding proteins. These domains are known as Ras association (RA) domains [RalGDS (Ral guanine nucleotide dissociation stimulator)/AF6 (ALL-1 fusion partner from chromosome 6)] and are distinct from Ras-binding domains (RBD) which bind an alternative set of Ras effectors [1, 2]. In addition to an RA domain, the classical RASSF proteins have a protein-protein interaction motif known as the SARAH domain that is responsible for scaffolding and regulatory interactions [8]. The best described protein in this family with respect to DNA damage is RASSF1 the review will concentrate on this protein with particular reference to a recently elucidated signalling network from RASSF1A and the potential clinical significance of targeting this pathway [13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
