Disease relevance of PRELP

• PRELP, collagen, and a theory of Hutchinson-Gilford progeria [1].

High impact information on PRELP

• The leucine-rich repeat protein PRELP binds perlecan and collagens and may function as a basement membrane anchor [2].
• Confocal immunohistochemistry showed that PRELP outlines basement membranes with a location adjacent to perlecan [2].
• We also found that PRELP binds collagen type I and type II through its leucine-rich repeat domain [2].
• As expected, truncated PRELP, without the heparin-binding domain, did not bind perlecan [2].
• Based on the location of PRELP and its interaction with perlecan heparan sulfate chains and collagen, we propose a function of PRELP as a molecule anchoring basement membranes to the underlying connective tissue [2].

Biological context of PRELP

• The human PRELP gene lacks a TATA box, and in its absence a Sp1-binding site residing 29 bp upstream of the transcription start site is essential for initiating gene expression [3].
• The 5'-flanking region of the human proline/arginine-rich end leucine-rich repeat protein (PRELP) gene has been characterized for both promoter and repressor activity by using a variety of reporter gene constructs and transient transfection into chondrocytes or fibroblasts [3].
• The putative roles of these proteins range from involvement in matrix organization or matrix-cell signaling (PRELP, chondroadherin, cartilage oligomeric protein and cartilage matrix protein) through to molecules that are likely to be involved with modulation of the chondrocyte phenotype (CD-RAP, CDMPs, chondromodulin and pleiotrophin) [4].
• The gene organization, chromosome location, and expression of a 55-kDa matrix protein (PRELP) of human articular cartilage [5].
• Hutchinson-Gilford progeria has been diagnosed in twins with a chromosomal inversion at, or very near, the site of the PRELP gene [1].

Anatomical context of PRELP

• Small leucine rich repeat proteoglycans (SLRPs) in the human sclera: identification of abundant levels of PRELP [6].
• The primary structure of a basic leucine-rich repeat protein, PRELP, found in connective tissues [7].
• The factor was not detected in nuclear protein preparations from adult chondrocytes in which the PRELP gene is expressed [3].

Associations of PRELP with chemical compounds

• Further analysis of PRELP in the human sclera by western blot analysis indicated that PRELP contained a 45 kDa core protein with short unsulfated keratan sulfate side chains and appeared in greatest abundance in sclera during the fourth decade of life [6].
• Characterization of the human proline/arginine-rich end leucine-rich repeat protein (PRELP) gene promoter and identification of a repressor element [3].

Other interactions of PRELP

• RESULTS: Semi-quantitative and quantitative PCR analysis showed that all six SLRPs were expressed in the human sclera, with PRELP exhibiting the highest steady state mRNA levels, relative to that of the other SLRPs (p<0.001, ANOVA) [6].
• The dissociation constants of the PRELP-perlecan interactions were in the range of 3-18 nm as determined by surface plasmon resonance [2].
• Bacterial killing by heparin-binding peptides from PRELP and thrombospondin [8].

Analytical, diagnostic and therapeutic context of PRELP

• Additionally, the protein expression and distribution of the SLRP family member, PRELP, was determined in the human sclera through western blot detection and immunohistochemistry [6].
• Electron microscopy visualized a complex with PRELP binding simultaneously to the triple helical region of procollagen I and the heparan sulfate chains of perlecan [2].

References