Expression and role of RIP140/NRIP1 in chronic lymphocytic leukemia

Abstract

RIP140 is a transcriptional coregulator, (also known as NRIP1), which finely tunes the activity of various transcription factors and plays very important physiological roles. Noticeably, the RIP140 gene has been implicated in the control of energy expenditure, behavior, cognition, mammary gland development and intestinal homeostasis. RIP140 is also involved in the regulation of various oncogenic signaling pathways and participates in the development and progression of solid tumors. During the past years, several papers have reported evidences linking RIP140 to hematologic malignancies. Among them, two recent studies with correlative data suggested that gene expression signatures including RIP140 can predict survival in chronic lymphocytic leukemia (CLL). This review aims to summarize the literature dealing with the expression of RIP140 in CLL and to explore the potential impact of this factor on transcription pathways which play key roles in this pathology.

Figure 1

Structure of the RIP140 gene and protein. Schematic representations of the RIP140 gene and protein (not scaled). (Top panel) The two promoters are shown together with the four exons (E1 to E4) which are represented by small rectangles, the blue one corresponding to the RIP140 coding sequence. (Middle panel) The box represents the RIP140 molecule showing the four different repressive domains (RD). (Bottom panel) The different nuclear signaling pathways either inhibited (−) or stimulated (+) by RIP140 are indicated.

Figure 2

Prognostic value of RIP140 in CLL patients. (A) Patients of the Herold’s cohort (n = 107) were ranked according to increasing RIP140 expression and a maximum difference in OS was obtained with an expression cutoff of 7.49 using the Maxstat R function. (B) Low RIP140 expression is associated with a shorter time to the first treatment in CLL patients. The data were normalized using the robust multichip average (RMA) method and Affymetrix gene expression data are publicly available via the online Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/) under accession number GSE22762, and GSE25571.