Disease relevance of LRP1B

• LRP1B was originally described as a putative tumor suppressor in lung cancer cells; however, its expression profile in several regions of adult human brain suggests it may have additional functions in the central nervous system [1].
• Frequent silencing of low density lipoprotein receptor-related protein 1B (LRP1B) expression by genetic and epigenetic mechanisms in esophageal squamous cell carcinoma [2].
• LRP 1 B functions as a receptor for Pseudomonas exotoxin [3].

Psychiatry related information on LRP1B

• Consequently LRP1B expression could function to protect against the pathogenesis of Alzheimer's disease [1].

High impact information on LRP1B

• Genomic PCR experiments revealed homozygous deletions of LRP1B in additional ESC cell lines (total, 6 of 43; 14.0%) and in primary esophageal tumors (30 of 70; 42.9%) [2].
• Methylation of LRP1B was also detected in primary esophageal tumors [2].
• These results suggest that loss of LRP1B function in esophageal carcinogenesis most often occurs either by homozygous deletion or by transcriptional silencing through hypermethylation of its CpG island [2].
• Treatment with 5-aza-2'-deoxycytidine restored expression of LRP1B in those ESC lines [2].
• Histone acetylation status correlated directly with expression of LRP1B and inversely with the methylation status of the CpG island [2].

Biological context of LRP1B

• A functional consequence of mLRP1B4 expression was a significant accumulation of APP at the cell surface, which is likely related to the slow endocytosis rate of LRP1B [1].
• Interestingly, the kinetics of ligand endocytosis is distinctly different from that of LRP, with LRP1B exhibiting a markedly diminished internalization rate [4].
• In the course of a program to screen ESC cell lines for copy-number aberrations using array-based comparative genomic hybridization, we identified a homozygous deletion of LRP1B [2].
• Taken together, these results demonstrate that LRP1B can function as a negative regulator of uPAR regeneration and cell migration [5].
• For LHX2 and LRP1B, bisulfite sequencing, real-time reverse transcriptase-polymerase chain reaction and induction of gene expression following treatment with the demethylating agent, 5'-aza-2'-deoxycytidine, were confirmed [6].

Anatomical context of LRP1B

• In addition, tissue expression analysis reveals that the LRP1B gene is expressed in brain, thyroid, and salivary gland [4].
• By using RT-PCR, we found that, while mouse LRP1B expression is mostly restricted to the brain, human LRP1B expression is more widespread with highest expression levels detected in the brain, adrenal gland, salivary gland, and testis [7].
• LRP1B attenuates the migration of smooth muscle cells by reducing membrane localization of urokinase and PDGF receptors [8].
• METHODS AND RESULTS: Immunohistochemistry showed that LRP1B expression in human coronary arteries is localized to the intimal SMCs near the plaque surface as well as to medial SMCs [8].

Physical interactions of LRP1B

• Cell surface and internalization assays, in combination with coimmunoprecipitation experiments, showed that LRP1B binds and internalizes uPAR [8].

Enzymatic interactions of LRP1B

• Finally, we found that, unlike mouse LRP1B, human LRP1B is cleaved by furin [7].

Other interactions of LRP1B

• The putative tumor suppressor LRP1B, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein [4].
• CONCLUSIONS: LRP1B modulates the catabolism of uPAR and PDGFR, affecting the migration of SMCs [8].

References