Disease relevance of PDCD5

• Two single-nucleotide polymorphisms with linkage disequilibrium in the human programmed cell death 5 gene 5' regulatory region affect promoter activity and the susceptibility of chronic myelogenous leukemia in Chinese population [1].
• In this study, human PDCD5 was expressed in Escherichia coli cell and studied using heteronuclear NMR method [2].
• Association of the PDCD5 locus with lung cancer risk and prognosis in smokers [3].
• Decreased expression of PDCD5 has been detected in various human carcinomas [4].
• Although PDCD5 is reducibly expressed in various human tumors, it is not clear which expression level of PDCD5 is in gastric cancer (GC) [5].

High impact information on PDCD5

• Here we show that PDCD5 has a remarkable role in intercellular transport in various cells (endogenous caveolin-1-positive and -negative cells) through a clathrin-independent endocytic pathway that originates from heparan sulfate proteoglycan binding and lipid rafts [6].
• However, it was found that recombinant PDCD5 added exogenously to culture medium could also enhance programmed cell death triggered by certain stimuli [6].
• This is further supported by the findings that certain drugs that disrupt lipid rafts, compete with cell membrane heparan sulfate proteoglycans, or block the caveolae pathway, impair the PDCD5 internalization process [6].
• An alternative form of paraptosis-like cell death, triggered by TAJ/TROY and enhanced by PDCD5 overexpression [7].
• RESULTS: Two SNPs were identified within the PDCD5 promoter [1].

Chemical compound and disease context of PDCD5

• A novel human TF-1 cell apoptosis-related protein, TFAR19, cloned from a human leukemia cell line, TF-1, was first overexpressed in Escherichia coli with the sequence Met-Gly-His(6)-Gly-Thr-Asn-Gly, a hexahistidine sequence followed by a hydroxylamine cleavage site attached to its amino terminus [8].

Biological context of PDCD5

• Luciferase reporter assays were carried out to show the functional significance of the SNPs located in the promoter region to PDCD5 expression [1].
• PDCD5 expression analysis in mononuclear cells derived from CML patients and cell lines with different -27/-11 genotypes showed consistent results with the reporter assays [1].
• In this report, we demonstrate that the level of PDCD5 protein expressed in cells undergoing apoptosis is significantly increased compared with normal cells, then the protein translocates rapidly from the cytoplasm to the nucleus of cells [9].
• The appearance of PDCD5 in the nuclei of apoptotic cells precedes the externalization of phosphatidylserine and fragmentation of chromosome DNA [9].
• To clarify whether expression of the programmed cell death 5 (PDCD5) gene in leukemic cells is abnormal, real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) was used to examine its expression in marrow cells from leukemia patients [10].

Anatomical context of PDCD5

• The apoptosis activity assay shows that the deletion of the N-terminal alpha-helix of PDCD5 significantly attenuates the apoptosis-promoting effects on HL-60 cells induced by serum withdrawal [11].
• PDCD5-positive chondrocytes were mainly distributed in the superficial and deep zones of OA tissue sections, as opposed to, in the superficial and middle regions of normal healthy tissue sections [12].
• Suppressed expression of PDCD5 attenuates the release of cytochrome c from mitochondria to cytosol induced by Bax overexpression [4].
• Transfer of anti-TFAR19 monoclonal antibody into HeLa cells by in situ electroporation can inhibit the apoptosis [13].
• After transfected with TFAR19 and apoptosis inducement, MEL revealed a high cell membrane fluidity, a decrease in resynthesis of phospholipids, an increase in the proteins/nucleic acids ratio, a relatively orderly cytoskeleton network, an impaired deformability, a low integrin aM expression, and a decrease in adhesion to endothelial cells [14].

Associations of PDCD5 with chemical compounds

• Treatment with the ABL tyrosine kinase inhibitor Imatinib mesylate increased PDCD5 expression in K562 and MEG-01 cells [10].
• The binding constant of the interaction between PDCD5 and heparin was calculated as 4.17 x 10(4) M(-1) by Scatchard analysis [15].
• After cleavage of the purified His(6)-tagged TFAR19 sample with hydroxylamine, highly purified untagged TFAR19 protein was then obtained through an FPLC Resource Q column [8].

Analytical, diagnostic and therapeutic context of PDCD5

• Real-time quantitative PCR and Western blot analysis were done to determine the expression differences of PDCD5 in CML patients with different genotypes [1].
• Expression of PDCD5 was detected by flow cytometry, immunofluorescence, RT-PCR and immunohistochemical analysis [12].
• In this study, we have systematically employed the approaches of RT-PCR, Real- time PCR, Immunohistochemistry (IHC), Immunofluorescence staining (IFS) and Western blot to determine the PDCD5 expression in GC cells and primary tumors, at mRNA and protein level, respectively [5].
• This study shows that TFAR19 may be a critical factor for apoptosis; and transfer of monoclonal antibody into mammalian cells by in situ electroporation is a useful method to study the function of endogenous factors [13].
• These findings suggest the potential of TFAR19 for antitumor cell migration, and thus for antitumor gene therapy [14].

References