Disease relevance of PERP

• Differential expression of PERP was identified in primary choroidal melanoma specimens, both at transcriptional and protein level [1].
• At the scene of ischemic brain injury: is PARP a perp [2]?
• The THW mutant had a 5- to 10-fold increase in activity on various CD22-positive cell lines and was up to 50 times more cytotoxic to cells from patients with chronic lymphocytic leukemia and hairy-cell leukemia [3].
• The HBD-2 gene and protein are locally expressed in keratinocytes associated with inflammatory skin lesions such as psoriasis as well as in the infected lung epithelia of patients with cystic fibrosis [4].
• Focal adhesion kinase is expressed in acantholytic keratinocytes associated with pemphigus vulgaris and pemphigus foliaceus [5].

High impact information on PERP

• Like PMP-22/gas3, PERP is a plasma membrane protein, and importantly, its expression causes cell death in fibroblasts [6].
• Taken together, these data suggest that PERP is a novel effector of p53-dependent apoptosis [6].
• Keratinocytes-associated chemokines and enzymatically quiescent heparanase induce the binding of resting CD4+ T cells [7].
• Ranked by PERP, these chemicals are: ethylene dibromide, ethylene dichloride, 1,3-butadiene, tetrachloroethylene, propylene oxide, chloroform, formaldehyde, methylene chloride, dioxane, and benzene [8].
• As PERP is a novel type of p53 effector that is likely to stimulate apoptosis through a mechanism distinct from that of Bcl-2-related mitochondrial effectors, further elucidation of its role in uveal melanoma pathogenesis will assist in the design of novel therapeutic approaches aimed at increasing the rate of apoptosis in this tumor [1].

Biological context of PERP

• Transcriptional downregulation of PERP did not present a statistically significant association with ciliary body involvement, size, PAS-positive loops or cell type [1].
• The transcriptional level of PERP gene was measured by quantitative real-time RT-PCR in 26 uveal melanomas with known chromosomes 3 and 8 status [1].
• Immunoblotting and immunohistochemistry further demonstrated significantly reduced PERP protein level in monosomy 3 melanomas, as compared with disomy 3 tumors [1].
• Identification of THW, a putative new tumor suppressor gene [9].
• It possesses an S-adenosylmethionine binding site and double E and THW loops, common and absolute features associated with other PRMTs [10].

Anatomical context of PERP

• For the left hippocampus, the mean volume was 3.29 cm3 (NOPERP protocol), 4.02 cm3 (REFOR protocol), and 3.74 cm3 (PERP protocol) [11].
• Down-regulation of THW is correlated with metastatic capacity of melanoma cell lines [9].
• Because these CD8+ T cells have a cytotoxic potential, they may contribute to the necrosis of keratinocytes associated with drug-induced blister formation [12].
• These data and the fact that the recently identified murine homologue PERP of gene THW mediates cell death in murine fibroblasts support the possible tumor suppressor function of gene THW [13].
• We have detected LOH for gene THW in cell lines derived from melanoma, breast, pancreas, cervical, prostate and colon carcinoma with different prevalence, whereas the ovary carcinoma cell lines (n = 3) were negative [13].

Other interactions of PERP

• Polymorphisms in the AKT1 and Perp genes significantly affect the frequency of apoptosis [14].
• Using a combination marker approach, levels of PERP, S100A2, and SPRR3 allowed discrimination of pathCR from < pathCR with high sensitivity and specificity (85%) [15].
• The potential of PERP, S100A2, and SPRR3 as biomarkers of pathCR warrants further validation [15].
• Expression of p53-induced apoptosis effector PERP in primary uveal melanomas: Downregulation is associated with aggressive type [1].
• Reduced PERP mRNA level was significantly associated with monosomy 3 (two-way ANOVA and t-test, p=0.004) but not with gains in chromosome 8 [1].

Analytical, diagnostic and therapeutic context of PERP

• PERP protein levels were assessed by Western blot analysis of 22 fresh-frozen tumors and by immunohistochemical analysis of 16 paraffin-embedded tumor specimens [1].

References