P53 Apoptosis Effector Related To PMP-22 Research Articles

DCAF13 promotes breast cancer cell proliferation by ubiquitin inhibiting PERP expression.

Evolutionarily conserved DDB1‐and CUL4‐associated factor 13 (DCAF13) is a recently discovered substrate receptor for the cullin RING‐finger ubiquitin ligase 4 (CRL4) E3 ubiquitin ligase that regulates cell cycle progression. DCAF13 is overexpressed in many cancers, although its role in breast cancer is currently elusive. In this study we demonstrate that DCAF13 is overexpressed in human breast cancer and that its overexpression closely correlates with poor prognosis, suggesting that DCAF13 may serve as a diagnostic marker and therapeutic target. We knocked down DCAF13 in breast cancer cell lines using CRISPR/Cas9 and found that DCAF13 deletion markedly reduced breast cancer cell proliferation, clone formation, and migration both in vitro and in vivo. In addition, DCAF13 deletion promoted breast cancer cell apoptosis and senescence, and induced cell cycle arrest in the G1/S phase. Genome‐wide RNAseq analysis and western blotting revealed that loss of DCAF13 resulted in both mRNA and protein accumulation of p53 apoptosis effector related to PMP22 (PERP). Knockdown of PERP partially reversed the hampered cell proliferation induced by DCAF13 knockdown. Co‐immunoprecipitation assays revealed that DCAF13 and DNA damage‐binding protein 1 (DDB1) directly interact with PERP. Overexpression of DDB1 significantly increased PERP polyubiquitination, suggesting that CRL4DCAF13 E3 ligase targets PERP for ubiquitination and proteasomal degradation. In conclusion, DCAF13 and the downstream effector PERP occupy key roles in breast cancer proliferation and potentially serve as prognostics and therapeutic targets.

Pilot study of loss of the p53/p63 target gene PERP at the surgical margin as a potential predictor of local relapse in head and neck squamous cell carcinoma.

PERP (p53 apoptosis effector related to PMP22) localizes to desmosomes and suppresses squamous cell carcinoma development. Loss of PERP leads to worse local control in head and neck squamous cell carcinoma (HNSCC), likely by destabilizing desmosomes. We evaluated PERP loss at HNSCC surgical margins as a predictor of local relapse. Combining discovery (n = 17) and validation (n = 31) cohorts, we examined membranous PERP protein expression by immunohistochemistry in surgical mucosal margins with competing risk analysis of the relationship between local relapse and PERP expression. Of the 44 analyzable patients, the 2-year cumulative incidence of local relapse was 44.4% for the PERP-negative group and 16.4% for the PERP-positive group (P = .01). A trend toward worse progression-free survival (P = .09) and overall survival (P = .06) was observed with loss of PERP. PERP loss at surgical margins is associated with higher risk of local recurrence in HNSCC, warranting further evaluation in a larger prospective study.

Mkrn2 deficiency induces teratozoospermia and male infertility through p53/PERP-mediated apoptosis in testis.

The apoptosis that occurs in the immature testis under physiological conditions is necessary for male germ cell development, whereas improper activation of apoptosis can impair spermatogenesis and cause defects in reproduction. We previously demonstrated that in mice, the makorin-2 (Mkrn2) gene is expressed exclusively in the testis and its deletion leads to male infertility. To understand the potential molecular mechanism, in this study, we found that levels of apoptosis in the testis were abnormally high in the absence of Mkrn2. To identify specific gene(s) involved, we performed digital gene expression profiling (DGE) and pathway analysis via gene set enrichment analysis (GSEA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and we found that MKRN2 inhibits p53 apoptosis effector related to PMP22 (PERP) expression and that levels of the protein in sperm samples have an inverse correlation with infertility levels. GSEA additionally indicated that PERP is a negative regulator of spermatogenesis and that its ectopic expression induces male infertility. Further, Gene Expression Omnibus (GEO) dataset analysis showed that p53, upstream of PERP, was upregulated in oligoasthenoteratozoospermia (OAT). These observations suggest that Mkrn2 is crucial for protecting germ cells from excessive apoptosis and implicate Mkrn2-based suppression of the p53/PERP signaling pathway in spermatogenesis and male fertility.

Epigenetic activation of PERP transcription by MKL1 contributes to ROS-induced apoptosis in skeletal muscle cells

Excessive reactive oxygen species (ROS) causes irreparable damages to cells and commit cells to programmed cell death or apoptosis. A panel of well-documented pro-apoptotic genes, including p53 apoptosis effector related to PMP-22 (PERP), are up-regulated and collectively mediate ROS induced apoptosis. The epigenetic mechanism whereby ROS stimulates PERP transcription, however, lacks in-depth characterization. Here we report that the transcriptional modulator megakaryocytic leukemia 1 (MKL1) is activated by H2O2 treatment in skeletal muscle cells (C2C12). Small interfering RNA (siRNA) mediated silencing or small-molecule compound (CCG-1423) mediated inhibition of MKL1 attenuated H2O2 induced apoptosis of C2C12 cells. Over-expression of MKL1 potentiated trans-activation of PERP whereas MKL1 ablation/inhibition abrogated the induction of PERP by H2O2 in C2C12 cells. Mechanistically, MKL1 interacted with and was recruited to the PERP promoter by the transcription factor E2F1. Once bound to the PERP promoter, MKL1 engaged the histone demethylase KDM3A to modulate the chromatin structure surrounding the PERP promoter thereby leading to PERP trans-activation. Depletion of either E2F1 or KDM3A blocked the induction of PERP by H2O2. In conclusion, our data illustrate a novel epigenetic pathway that links PERP transcription to ROS-induced apoptosis in skeletal muscle cells.

Abstract 62: Loss of PERP p53/p63 target gene may indicate tumorigenesis at the margin and local recurrence

Abstract Objectives: PERP (p53 apoptosis effector related to PMP22) localizes to the desmosomal adhesion complexes and is involved in suppressing squamous cell carcinoma (SCC) development. Loss of PERP expression leads to destabilization of desmosome complexes, resulting in enhanced tumor aggressiveness and worse local control in head and neck SCC (HNSCC). We had previously examined PERP loss at surgical margins in a small cohort of HNSCC patients. Results suggested that the loss of PERP may serve as a marker for persistent tumor and predictive of local relapse. Here we validate these findings in an independent patient cohort and report on the combined results of both groups. Materials and Methods: We previously examined the PERP protein expression by immunohistochemistry (IHC) in the surgical mucosal margins of 17 HNSCC patients. The validation cohort consists of 31 patients (15 oral cavity, 11 hypopharynx, 5 larynx). PERP expression was similarly assessed by IHC in the surgical margins of these patients. Finally, we combined the results of both groups to yield 48 patients with HNSCC (18 oral cavity, 12 hypopharynx, 4 oral pharynx, 14 larynx) for competing risk analysis. The relationship between local relapse and PERP expression (positive or negative) was analyzed in a competing risk model with death as a competing risk. Results: In the initial cohort, the 2-year cumulative incidence rate of local relapse was 37.5% for the negative PERP group compared to a 20% for the positive PERP group (p = 0.177). In the validation cohort, the 2-year cumulative incidence rate of local relapse was 50% for the negative PERP group compared to a 15% for the positive PERP group (p = 0.063). Since the results were similar between two groups, we combined them together for additional analyses. In this combined dataset, PERP expression was negative in 18, positive in 26, and not assessable in three patients. Of the 45 analyzable patients, the 2-year cumulative incidence rate of local relapse was 44.4% for the negative PERP group compared to a 16.4% for the positive PERP group (p = 0.010). There was also a trend for worse progression-free survival (p = 0.059) and overall survival (p = 0.085) with the loss of PERP. Conclusions: PERP loss at the surgical margins appears to be associated with a higher risk of local recurrence in HNSCC. These promising results need to be tested in a larger prospective study. Citation Format: Amanda Simmons, Christina Kong, Rie von Eyben, Laura Attardi, Xiaohui Ma, Quynh-Thu Le, Cherie-Ann Nathan. Loss of PERP p53/p63 target gene may indicate tumorigenesis at the margin and local recurrence [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 62.

Coactosin-like protein CLP/Cotl1 suppresses breast cancer growth through activation of IL-24/PERP and inhibition of non-canonical TGFβ signaling.

Coactosin-like protein (CLP, or Cotl1), is an F-actin-binding protein, whose role in cancer is largely unknown. Here we show that CLP/Cotl1 is highly expressed in a rat epithelial breast cancer cell line (FE1.3) compared with its mesenchymal counterpart (FE1.2). Knockdown of CLP/Cotl1 in FE1.3 cells increased cell proliferation, whereas its overexpression in FE1.2 cells inhibited proliferation in culture and reduced tumor growth in xenograft assays in mice. Mechanistically, we identified two major pathways through which CLP/Cotl1 exerts its suppressive effects. First, CLP/Cotl1 re-expression in FE1.2 and in human MCF7 breast cancer cells induced expression of the growth-suppressor gene interleukin-24 (IL-24), which independently of p53 upregulates the tumor-suppressor genes p53 apoptosis effector related to PMP-22 (PERP) and p21cip1. Second, overexpression of CLP/Cotl1 potentiated the growth-suppressive effect of transforming growth factor-β1 (TGFβ1), leading to downregulation of TGFβ-responsive genes vascular growth factor A/B (VEGFA/VEGFB), hypoxia inducing factor 1α (HIF-1α) and trombospondin 1 (TSP1), which mediate various hallmarks of cancer progression including angiogenesis, invasion and metastasis. CLP/Cotl1 inhibited TGFβ signaling via a non-canonical signaling involving IL-24-instigated inhibition of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) phosphorylation and subsequent post-transcriptional downregulation of SMAD2 and SMAD4. We also showed that CLP/COTL1 expression sensitizes breast cancer cells to chemotherapeutic drugs, and this was further enhanced by addition of exogenous TGFβ1. CLP/Cotl1 expression is lost in many human malignancies including prostate, uterine and breast cancers. Thus, our results uncover a novel tumor-suppressor role for CLP/Cotl1 and identify the downstream effectors interleukin 24 (IL-24)/PERP and IL-24/MAPK/ERK/TGFβ as potential targets for precision therapy.

P63 is required beside p53 for PERP-mediated apoptosis in uveal melanoma.

Background:PERP (p53 apoptosis effector related to PMP-22), a transcriptional target of p53, is downregulated and contributes to the impairment of apoptosis in uveal melanoma (UM). Intriguingly, PERP is not induced in UM despite functional p53. p63, located on chromosome 3, which is characteristically altered in high-risk UM, can transactivate PERP. Here, we determine the functional role of p63 expression in the initiation of p53/PERP-mediated apoptosis in UM.Methods:PERP expression was monitored by quantitative PCR (qPCR) and immunoblotting in UM cell lines treated with DNA-damaging agents. The functional role of p63 was assessed by transient expression of p63-turbo GFP (p63-tGFP) in the apoptosis- resistant, 3q-deficient OCM-1 cells. Expression and localisation of p63, PERP and p53, and induction of apoptosis were characterised by qPCR, immunoblotting and live cell confocal microscopy.Results:PERP expression was significantly downregulated in all UM cell lines. DNA-damaging treatments failed to induce apoptosis and activate PERP in OCM-1 cells, which displayed non-functional levels of p63. Expression of p63-tGFP induced apoptosis with marked increase in PERP expression and associated p53 accumulation.Conclusions:Lack of p63 contributes to reduced PERP levels and impaired p53-mediated apoptosis in UM. p63 expression is required for PERP-mediated apoptosis in UM.

Transmembrane protein PERP is a component of tessellate junctions and of other junctional and non-junctional plasma membrane regions in diverse epithelial and epithelium-derived cells

Protein PERP (p53 apoptosis effector related to PMP-22) is a small (21.4 kDa) transmembrane polypeptide with an amino acid sequence indicative of a tetraspanin character. It is enriched in the plasma membrane and apparently contributes to cell-cell contacts. Hitherto, it has been reported to be exclusively a component of desmosomes of some stratified epithelia. However, by using a series of newly generated mono- and polyclonal antibodies, we show that protein PERP is not only present in all kinds of stratified epithelia but also occurs in simple, columnar, complex and transitional epithelia, in various types of squamous metaplasia and epithelium-derived tumors, in diverse epithelium-derived cell cultures and in myocardial tissue. Immunofluorescence and immunoelectron microscopy allow us to localize PERP predominantly in small intradesmosomal locations and in variously sized, junction-like peri- and interdesmosomal regions (“tessellate junctions”), mostly in mosaic or amalgamated combinations with other molecules believed, to date, to be exclusive components of tight and adherens junctions. In the heart, PERP is a major component of the composite junctions of the intercalated disks connecting cardiomyocytes. Finally, protein PERP is a cobblestone-like general component of special plasma membrane regions such as the bile canaliculi of liver and subapical-to-lateral zones of diverse columnar epithelia and upper urothelial cell layers. We discuss possible organizational and architectonic functions of protein PERP and its potential value as an immunohistochemical diagnostic marker.

Burkitt Lymphoma Specific Zinc Finger Protein ZNF385B Is Involved in Regulation of B Cell Apoptosis

Abstract 1584Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) are common types of childhood mature B-cell non-Hodgkin's lymphoma (NHL). Both are postulated to be derived from GC B-cells but they are independent disease entities of NHL; however, they have overlapping morphologic and immunophenotypic features. A characteristic translocation t(8;14) of BL also occurs in 5 to 10 percent of cases of DLBCL. It is not uncommon to have difficulty in differentiating BL from DLBCL at initial diagnosis. Therefore, the latest WHO classification of tumors of the lymphoid tissue has recognized a category with overlapping features between BL and DLBCL. Considering this background, gene-expression profiling using microarray should provide an accurate, quantitative method for distinguishing the NHL. Actually, other researchers performed gene-expression profiling of mature B-cell lymphoma at all ages and showed that BL could be reliably distinguished from DLBCL. It has also been reported that DLBCL can be classified into two categories of patients with very different five-year overall survival rates on the basis of gene-expression profile.In an attempt to investigate the molecules specifically expressed in each type of NHL, we performed the screening of genes expressed characteristically in each type of childhood hematologic malignancy by employing a microarray system using clinical specimens from pediatric patients, consisting of 3 patients with DLBCL, 16 with BL, 6 with BCP-ALL and 6 with T-ALL. Consistent with previous reports, CD40, EBI3, FGD6, LMO2, and SERPINA9 were over-expressed in DLBCL. In addition, over-expression of IL21R, STAT3, BCL6, CD58, JAK3 was observed in DLBCL. In BL, on the other hand, BMP7 and SOX11 were over-expressed as reported previously. Furthermore, we found that ZNF385B, BMP3, PEG10, MUC4, AICDA, SMAD1, C13orf15, CD24 were over-expressed in BL.In these candidate genes, ZNF385B, also called ZNF533, was expressed in vast majority of BL cases as well as BL cell lines but not in other hematopoietic malignancies, including DLBCL, B-cell precursor ALL, and mature B-cell malignancies originate from another developmental stages of B cells. Therefore, we concluded that ZNF385B is a BL-specific zinc-finger protein and can be used as a diagnostic marker for BL.Currently three isoforms (IFs) of ZNF385B have been identified and IF-1 is the longest transcript variant, which possesses 4 ZF domains, while IF-2/3 are shorter transcript variants with 3 ZF domains. Although the function and biological significance of this protein have not been clarified at all, ZNF385A has high homology with ZNF385B IF-2/3 is known to be involved in apoptosis regulation. Therefore, we intended to elucidate the functional role of ZNF385B in B cells.First we analyzed intracellular localization of ZNF385B. When ZNF385B IF-1 proteins fused with EGFP at the N-terminus were expressed transiently in DLBCL BJAB cells, we observed the nuclear localization by obtaining fluorescent images.Next, to examine the characteristics of ZNF385B, we established a protein inducible system in a tetracycline-dependent manner for both ZNF385B IF-1 and its deletion mutant ZNF385B-DEL corresponds to IF-2/3 lacking ZF domain in N-terminus in BJAB cells. Interestingly, ectopic expression of ZNF385B IF-1 induced up-regulation of PERP (p53 apoptosis effector related to PMP-22) and activation of caspase-3 and −8, resulting in apoptosis induction, whereas ZNF385B-DEL did not. Furthermore, ZNF385B-DEL inhibited apoptosis induced by CD20 cross-linking and BCR stimulation. Immunoprecipitation by anti-p53 antibody indicated the binding of ZNF385B isoform 1 with p53. Since PERP is known to be a p53 transcriptional target, these results suggest the involvement of ZNF385B in B-cell apoptosis by modulating p53 transactivation. Considering our observation of ZNF385B expression in a portion of cells in peripheral lymphoid organs, ZNF385B possibly is involved in the regulation of death and survival that specifically occurs in germinal center B cells. Disclosures:No relevant conflicts of interest to declare.

PERP expression stabilizes active p53 via modulation of p53-MDM2 interaction in uveal melanoma cells

The activation and regulation of target genes by the tumour-suppressor p53 dictates the fate of a cell, with cell cycle arrest or apoptosis being two distinct outcomes. PERP (p53 apoptosis effector related to PMP-22), a p53 transcriptional target, is induced specifically during apoptosis but not cell cycle arrest. Downregulation of PERP is associated with the aggressive, monosomy 3-type of uveal melanoma (UM), the most common primary intraocular tumour in adults, and increased PERP expression has a pro-apoptotic effect in UM cells. Here, we identify a novel effect of PERP expression, as elevated PERP protein positively influences active levels of its own transcriptional regulator, p53. Using fluorescent fusion proteins of PERP, p53 and MDM2, we demonstrate in single living UM cells that PERP expression significantly enhances p53 activity and its nuclear localization, increases p53-dependent transcription (including that of MDM2) while allowing oscillatory nucleo-cytoplasmic shuttling of p53/MDM2 complexes. Phosphorylation of p53 serine residues that interfere with the interaction between p53 and its negative regulator MDM2 and enhance pro-apoptotic gene transcription also occurs subsequent to PERP expression. These results implicate a role for PERP in amplifying functional p53 levels that promote p53-dependent apoptosis, and reveal a potential target for exploitation in enhancing p53 activity.

PERP, a p53 proapoptotic target, mediates apoptotic cell death in renal ischemia

The p53 tumor suppressor gene plays a crucial role in mediating apoptotic cell death in renal ischemia-reperfusion injury (IRI). To further elucidate the p53-dependent pathway, we investigated the role of the p53 apoptosis effector related to PMP-22 (PERP), an apoptosis-associated p53 transcriptional target. PERP mRNA and protein are highly induced in the outer medullary proximal tubular cells (PTC) of ischemic kidneys postreperfusion at 3, 12, and 24 h in a p53-dependent manner. In PTC, overexpression of PERP augmented the rate of apoptosis following hypoxia by inducing mitochondrial permeability and subsequent release of cytochrome c, apoptosis-inducing factor (AIF), and caspase 9 activation. In addition, silencing of the PERP gene with short hairpin RNA prevented apoptosis in hypoxia-mediated injury by precluding mitochondrial dysfunction and consequent cytochrome c and AIF translocation. These data suggest that PERP is a key effector of p53-mediated apoptotic pathways and is a potential therapeutic target for renal IRI.

P53 apoptosis mediator PERP: localization, function and caspase activation in uveal melanoma

p53 apoptosis effector related to PMP-22 (PERP) is a transcriptional target gene of p53 tumour suppressor that is specifically induced during apoptosis and not during cell cycle arrest. In primary uveal melanoma (UM), the most common intraocular malignancy in adults that has a reportedly unaffected signalling pathway upstream of and including p53, PERP expression is down-regulated in the metastatic monosomy 3-type tumours, compared with the less aggressive disomy 3-type tumours. Here, we demonstrate experimentally, by the use of full-length PERP-green fluorescent protein (GFP) fusions and real-time confocal microscopy, the intracellular targeting and plasma membrane localization of PERP in living UM cells and show that expression of PERP induces caspase-mediated apoptosis in UM cells. Induction of PERP expression in GFP-PERP-transfected UM cells leads to increased levels of cleaved caspase-8 forms, as well as to reduction of its full-length substrate Bid, but not to detectable processing of caspase-9. The levels of mature caspase-8, -9 and -3 proteins significantly correlate with PERP expression levels in primary UMs. Transcriptional profiling of PERP and caspase-8 in tumour specimens indicates that the positive association of PERP and caspase-8 proteins is a consequence of post-translational processing, most likely at the level of caspase-8 cleavage, and not of increased transcription of pro-caspase-8. We conclude that PERP expression leads to activation of an extrinsic receptor-mediated apoptotic pathway, with a possible subsequent engagement of the intrinsic apoptotic pathway. The findings underline the apoptotic pathway mediated by PERP as a critical mechanism employed by UM tumours to modulate susceptibility to apoptosis.

Expression of p53-induced apoptosis effector PERP in primary uveal melanomas: Downregulation is associated with aggressive type

Expression of PERP ( p53 apoptosis effector related to PMP-22) was investigated in primary uveal melanomas and its variation was analyzed in relation to clinico-pathological and cytogenetical characteristics of these tumors. 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. PERP protein levels were assessed by Western blot analysis of 22 fresh-frozen tumors and by immunohistochemical analysis of 16 paraffin-embedded tumor specimens. Differential expression of PERP was identified in primary choroidal melanoma specimens, both at transcriptional and protein level. 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. Transcriptional downregulation of PERP did not present a statistically significant association with ciliary body involvement, size, PAS-positive loops or cell type. Immunoblotting and immunohistochemistry further demonstrated significantly reduced PERP protein level in monosomy 3 melanomas, as compared with disomy 3 tumors. The altered expression of PERP highlighted this apoptosis-specific target of p53 as a possible contributor to apoptosis in uveal melanoma with PERP downregulation being particularly relevant to the aggressive (monosomy 3) type of uveal melanoma. 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.

A Perpetrator of p53-dependent Apoptosis

STKE The activation of the tumor suppressor protein p53 can lead to cell cycle arrest or to apoptosis. Attardi et al. used subtractive hybridization to identify a gene involved specifically in the p53-dependent apoptosis pathway; PERP (p53 apoptosis effector related to PMP-22) was induced in p53-mediated apoptosis of mouse embryonic fibroblasts, but not in p53-deficient fibroblasts and not in UV-triggered apoptosis. The PERP promoter contained two putative p53 binding sites, and expression of PERP in p53-null cells resulted in cell death, suggesting that this newly identified protein may lie downstream of p53. PERP shares sequence similarity to PMP-22/gas3, a group of plasma membrane proteins connected to human demyelinating peripheral neuropathies such as Charcot-Marie-Tooth.— JN Genes Dev. 14 , 704 (2000).

A p53-dependent Apoptosis Perpetrator

The activation of p53 can lead to cell-cycle arrest or apoptosis. Attardi et al . used subtractive hybridization to identify genes involved in the p53-dependent apoptosis pathway. They identified a gene called p53 apoptosis effector related to PMP-22 (PERP) that is expressed in p53-mediated apoptosis of mouse embryonic fibroblasts (MEFs), but not expressed in p53-deficient MEFs. Transfection of luciferase vectors containing the PERP promoter into wild-type and p53-deficient MEFs revealed that the PERP promoter was activated in a p53-dependent manner, through p53 response elements. Fluorescence assays indicated that PERP localizes to the Golgi complex and, to a lesser extent, the plasma membrane. In the absence of p53, overexpression of PERP led to apoptosis of MEFs. Expression of Bcl-2 inhibited apoptosis induced by overexpressed PERP without affecting the amount of PERP expressed. Thus, p53-induced expression of PERP may be sufficient to cause apoptosis. PERP shares sequence similarity to the PMP-22/gas3 family of tetraspanins, a group of plasma membrane proteins whose mutations are thought to lead to human neuropathies such as Charcot-Marie-Tooth. Attardi, L.D., Reczek, E.E., Cosmas, C., Demicco, E.G., McCurrach, M.E., Lowe, S.W., and Jacks, T. (2000) PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family. Genes Dev . 14 : 704 -718. [Abstract] [Full Text]