geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Inhibition of heat shock protein 27-mediated resistance to DNA damaging agents by a novel PKC delta-V5 heptapeptide


, : Inhibition of heat shock protein 27-mediated resistance to DNA damaging agents by a novel PKC delta-V5 heptapeptide. Cancer Research 67(13): 6333-6341

Heat shock protein 27 (HSP27), which is highly expressed in human lung and breast cancer tissues, induced resistance to cell death against various stimuli. Treatment of NCI-H1299 cells, which express a high level of HSP27, with small interference RNA specifically targeting HSP27 resulted in inhibition of their resistance to radiation or cisplatin, suggesting that HSP27 contributed to cellular resistance in these lung cancer cells. Furthermore, because HSP27 interacts directly with the COOH terminus of the protein kinase C delta (PKC delta)-V5 region with ensuing inhibition of PKC delta activity and PKC delta-mediated cell death, we wished to determine amino acid residues in the V5 region that mediate its interaction with HSP27. Investigation with various deletion mutants of the region revealed that amino acid residues 668 to 674 of the V5 region mediate its interaction with HSP27. When NCI-H1299 cells were treated with biotin or with FITC-tagged heptapeptide of the residues 668 to 674 (E-F-Q-F-L-D-I), the cells exhibited dramatically increased cisplatin or radiation-induced cell death with the heptapeptide having efficient interaction with HSP27, which in turn restored the PKC delta activity that had been inhibited by HSP27. In vivo nude mice grafting data also suggested that NCI-H1299 cells were sensitized by this heptapeptide. The above data strongly show that the heptapeptide of the PKC delta-V5 region sensitized human cancer cells through its interaction with HSP27, thereby sequestering HSP27. The heptapeptide may provide a novel strategy for selective neutralization of HSP27.

US$19.90

PMID: 17616692

DOI: 10.1158/0008-5472.CAN-06-4344


Other references

Lowry, S.F.; Foster, D.M.; Norton, J.A.; Berman, M.; Brennan, M.F., 1981: Glucose disposal and gluconeogenesis from alanine in tumor-bearing Fischer 344 rats. For the study of glucose carbon recycling and incorporation of carbon atoms from plasma glucose, [3-3H]glucose and [U-14C]alanine were injected into inbred non-tumor-bearing (NTB) and tumor-bearing (TB) male F344 rats. The glucose and alanine kine...

Soja Constance M.; Sunderlin David; Close Steven; White Brian, 2005: Eclosion fenetre and dinosaur egg taphonomy. PaleoBios 25(2, Suppl

Akaboshi, M.; Noda, M.; Kawai, K.; Maki, H.; Kawamoto, K., 1979: Asymmetrical radical formation in D- and L-alanines irradiated with yttrium-90 beta-rays. Radical formation in 90Y-beta-irradiated D- and L-alanines was studied using ESR. It was observed that the relative radical concentration by beta-irradiation was distinguishably (13.9-21.5%) more in D-alanine than in L-alanine. Discussion was made...

Fournier, A.; Shields, T.W.; Neil, R.P.; Hayes, C.M.; Papineau-Couture, G., 1968: Automated determination of estrogens in the urine of pregnant mares. Annals of the New York Academy of Sciences 153(2): 501-510

Hranilovic, D.; Stefulj, J.; Furac, I.; Kubat, M.; Balija, M.; Jernej, B., 2003: Serotonin transporter gene promoter (5-HTTLPR) and intron 2 (VNTR) polymorphisms in Croatian suicide victims. Background: Disturbances in serotonin (5HT) transmission are the most frequently reported neurobiological substrates of suicidal behavior. Because 5HT transporter plays a central role in the regulation of 5HT synaptic function and its gene contain...

Whitelaw, M.J.; Fox, L.P.; Schlichting, F.R., 1963: Results Of Treatment Of Trichomoniasis With Metronidazole (Flagyl) In Private And Clinic Patients. Western Journal of Surgery, Obstetrics, and Gynecology 71: 232-233

Lomangino, K., 2006: Breastfed infants still vitamin D-deficient in U.S. Nutrition and the MD 32(11): 7-8

Kurygin, A.A., 1973: Treatment of massive hemorrhages in duodenal ulcers by vagotomy. Vestnik Khirurgii Imeni I. I. Grekova 111(7): 21-24

Lewin, Victor, 1965: The introduction and present status of California quail in the Okanagan Valley of British Columbia. A survey conducted in 1963 showed that 250,000 quail occur in a 390 square mile area largely confined to a 95 mile-long strip of irrigated orchard land at elevations below 2000 feet from Vernon southward to the U.S. boundary. Extralimital records...

Arnold, R.D.; Slack, J.E.; Zhou, R.; Mazurchuk, R.V.; Chau, R.I.; Straubinger, R.M., 2003: Antivascular effect of doxorubicin liposomes in a rat brain tumor model. Proceedings of the American Association for Cancer Research Annual Meeting 44: 729, July