Abstract
The evolutionarily-conserved La-related protein (LARP) family currently comprises Genuine La, LARP1, LARP1b, LARP4, LARP4b, LARP6 and LARP7. Emerging evidence suggests each LARP has a distinct role in transcription and/or mRNA translation that is attributable to subtle sequence variations within their La modules and specific C-terminal domains. As emerging research uncovers the function of each LARP, it is evident that La, LARP1, LARP6, LARP7 and possibly LARP4a and 4b are dysregulated in cancer. Of these, LARP1 is the first to be demonstrated to drive oncogenesis. Here, we review the role of each LARP and the evidence linking it to malignancy. We discuss a future strategy of targeting members of this protein family as cancer therapy.
Highlights
Cancer is a disease on the rise, from a current worldwide incidence of 14 million cases per year to a predicted 25 million cases per year by 2030 [1]
LARP1 was associated with Raptor in conditions of normal mTORC1 activity and hypothesised that, upon phosphorylation of 4E-BP1 by Mammalian target of rapamycin (mTOR), eukaryote initiation factor 4E (eIF4E) returns to the eIF4F complex and LARP1 binds polyadenylate binding protein (PABP)
Assembly on terminal oligopyrimidine (TOP) mRNAs by directly binding the TOP oligopyrimidine motif via its DM15-repeat containing region also known as (DM15) region, but at the same time acting as a scaffold that brings mTORC1 to these proteins for their activation (i.e., 4E-BP1 phosphorylation, LARP1 phosphorylation and removal)
Summary
Cancer is a disease on the rise, from a current worldwide incidence of 14 million cases per year to a predicted 25 million cases per year by 2030 [1]. Biomolecules 2015, 5 from the recent discovery of immunotherapy strategies effective in melanoma and lung cancer [3], chemotherapy has remained the mainstay of systemic therapy since its introduction in the 1940s This is despite the information revolution that followed publication of the human genome sequence in 2001, against which the genomes of common cancers were compared leading to the development of specific, molecularly-targeted anti-cancer agents [4,5]. These drugs have dramatically improved survival from malignancies with driver mutations like HER2-positive breast cancer [6,7], melanoma [8] and renal cell cancer [9], their impact on others such as cancers of the stomach, brain, oesophagus and lung has been negligible [10]. We will discuss an evolutionarily conserved family of RBPs, the La related proteins (LARPs) that are associated with cancer
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