Proproliferative functions of Drosophila small mitochondrial heat shock protein 22 in human cells.
Aging is a complex process accompanied by a decreased capacity of cells to cope with random damages induced by reactive oxygen species, the natural by-products of energy metabolism, leading to protein aggregation in various components of the cell. Chaperones are important players in the aging process as they prevent protein misfolding and aggregation. Small chaperones, such as small heat shock proteins, are involved in the refolding and/or disposal of protein aggregates, a feature of many age-associated diseases. In Drosophila melanogaster, mitochondrial Hsp22 (DmHsp22), is localized in the mitochondrial matrix and is preferentially up-regulated during aging. Its overexpression results in an extension of life span (>30%) (Morrow, G., Samson, M., Michaud, S., and Tanguay, R. M. (2004) FASEB J. 18, 598-599 and Morrow, G., Battistini, S., Zhang, P., and Tanguay, R. M. (2004) J. Biol. Chem. 279, 43382-43385). Long lived flies expressing Hsp22 also have an increased resistance to oxidative stress and maintain locomotor activity longer. In the present study, the cross-species effects of Hsp22 expression were tested. DmHsp22 was found to be functionally active in human cells. It extended the life span of normal fibroblasts, slowing the aging process as evidenced by a lower level of the senescence associated beta-galactosidase. DmHsp22 expression in human cancer cells increased their malignant properties including anchorage-independent growth, tumor formation in nude mice, and resistance to a variety of anticancer drugs. We report that the DmHsp22 interacts and inactivates wild type tumor suppressor protein p53, which may be one possible way of its functioning in human cells.
Wadhwa
Renu
R
From the National Institute of Advanced Industrial Science and Technology, Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305 8562, Japan.
Ryu
Jihoon
J
From the National Institute of Advanced Industrial Science and Technology, Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305 8562, Japan; the Brain Korea 21 Project for Medical Science, Institute for Cancer Research, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, Korea.
Gao
Ran
R
From the National Institute of Advanced Industrial Science and Technology, Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305 8562, Japan.
Choi
Il-Kyu
IK
From the National Institute of Advanced Industrial Science and Technology, Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305 8562, Japan; the Graduate Program for Nanomedical Science, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul, Korea, and.
Morrow
Geneviève
G
the Laboratoire de Génétique Cellulaire et Développementale, Département de Médecine, PROTÉO, Pav. C.E.-Marchand, Université Laval, Quebec G1V 0A6, Canada.
Kaur
Kamaljit
K
From the National Institute of Advanced Industrial Science and Technology, Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305 8562, Japan.
Kim
Inwook
I
From the National Institute of Advanced Industrial Science and Technology, Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305 8562, Japan; the Graduate Program for Nanomedical Science, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul, Korea, and.
Kaul
Sunil C
SC
From the National Institute of Advanced Industrial Science and Technology, Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305 8562, Japan. Electronic address: s-kaul@aist.go.jp.
Yun
Chae-Ok
CO
the Brain Korea 21 Project for Medical Science, Institute for Cancer Research, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, Korea; the Graduate Program for Nanomedical Science, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul, Korea, and. Electronic address: chaeok@yuhs.ac.
Tanguay
Robert M
RM
the Laboratoire de Génétique Cellulaire et Développementale, Département de Médecine, PROTÉO, Pav. C.E.-Marchand, Université Laval, Quebec G1V 0A6, Canada. Electronic address: Robert.tanguay@rsvs.ulaval.ca.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D014162:Transfection; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D029721:Drosophila Proteins; D006360:Heat-Shock Proteins; C490752:Hsp22 protein, Drosophila; D024101:Mitochondrial Proteins; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D017239:Paclitaxel; D015739:Nocodazole