Abstract
Tumor suppressor gene product p53 in its wild-type conformation, is an effector of apoptosis. A rat histiocytic tumor, AK-5 which has a rearranged and mutated p53 gene undergoes apoptosis upon heat shock through surface expression of CD95 receptor. DNA sequence analysis of p53 gene from tumor cells revealed a deletion of āCā at nucleotide position 942 and an addition of āAā at position 1055. Deletion of one nucleotide caused premature termination of p53 protein which resulted in shorter p53 protein with an altered sequence from amino acids 315 to 341. Altered p53 was unable to protect BC-8, a single cell clone of AK-5 cells from apoptosis upon heat shock. BC-8 cells transfected with a wild-type p53gene (3B4 cells) were resistant to heat induced apoptosis and did not show the expression CD95 death receptor. Inhibition of p53 expression by using antisense oligo induced apoptosis upon heat shock in 3B4 cells. Similarly, inhibition of CD95 expression by antisense oligo inhibited heat induced apoptosis in BC-8 cells. In addition, cell cycle regulatory molecules, cdc2 and cdk2 are differentially regulated in a non-cell cycle dependent manner in these tumor cells. These results, in view of lack of heat shock response in BC-8 cells suggest a complex interaction between p53, CD95 and hsp70 which determines the fate of the cell. In the absence of functional p53, CD95 appears to be an effector of apoptosis in BC-8 cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Bennett M, Mac-donald K, Chan SW, Luzio JP, Simari R, Weissber JP . 1998 Science 282: 290ā293
Caelles C, Helmberg A, Karin M . 1994 Nature 370: 220ā223
Crook T, Marston MJ, Sara EA, Vousden KH . 1994 Cell 79: 817ā827
Debatins KM, Suss D, Krammer PH . 1994 Eur. J. Immunol. 24: 753ā758
Deshpande G, Leelakumari A, Khar A . 1990 FEBS. Lett. 271: 199ā202
El-Deiry WS . 1998 Sem. Cancer Biol. 8: 345ā357
Fourie AM, Hupp TR, Lane DP, Sang B-C, Barbosa MS, Sambrook JF, Gething M-JH . 1997 J. Biol. Chem. 272: 19471ā19479
Fukazawa T, Fujiwara T, Morimoto Y, Shao J, Nishizaki M, Kadowaki Y, Hizuta A, Owen-Schaub LB, Roth JA, Tanaka N . 1999 Oncogene. 18: 2189ā2199
Furukawa Y, Iwase S, Terui Y, Kikuchi J, Sakai T, Nakamura M, Kitagawa S, Kitagawa M . 1996 J. Biol. Chem. 271: 28469ā28477
Gil-Gomez G, Berns A, Brady HJM . 1998 EMBO. J. 17: 7209ā7218
Gong J, Traganos F, Darzynkiewicz Z . 1994 Anal. Biochem. 218: 314ā319
Hahne M, Rimoldi D, Schroter M, Romero P, Schreier M, French LE, Schneider P, Bornand T, Fontana A, Leinard D, Cerottini J, Tschopp J . 1996 Science 274: 1363ā1366
Jaattela M, Wissing D, Kokholm K, Kallunki T, Egeblad . 1998 EMBO. J. 17: 6124ā6134
Khar A, Ali AM . 1990 In Vitro Cell Dev. Biol. 26: 1024ā1025
Kim JM, Yoon YD, Tsang BK . 1999 Endocrinology 140: 2307ā2317
Ko LJ, Prives C . 1996 Genes Dev. 10: 1054ā1072
Krammer PH, Behrmann I, Daniel P, Dhein J, Debatin KM . 1994 Curr. Opin. Immunol. 6: 279ā289
Levine AJ . 1997 Cell 88: 323ā331
Morimoto RI . 1993 Science 259: 1409ā1410
Muller M, Wilder S, Bannasch D, Israeli D, Lehlbach K, Li-Weber M, Friedman SL, Galle PR, Stremmel W, Oren M, Krammer PH . 1998 J. Exp. Med. 188: 2033ā2045
Munsch D, Watanabe-Fukunaga R, Bourdon J-C, Nagata S, May E, Yonish-Rouach E, Reisdorf P . 2000 J. Biol. Chem. 275: 3867ā3872
Murayama Y, Terao K, Inoue-Murayama M . 2000 Hum. Immunol. 61: 474ā485
Nagata S . 1994 Adv. Immunol. 57: 129ā144
Nagata S, Goldstein P . 1995 Science 267: 1449ā1456
Nagata S . 1997 Cell 88: 355ā365
Owen-Schaub LB, Zhang W, Cusack JC, Angelo LS, Santee SM, Fujiwara T, Roth JA, Deisseroth AB, Zhang WW, Kruzel E, Radinsky R . 1995 Mol. Cell Biol. 15: 3032ā3040
Pardhasaradhi BVV, Khar A . 1996 Ind. J. Exptl. Biol. 34: 945ā948
Raff M . 1992 Nature 343: 76ā79
Robinson JP, Darzynkiewicz Z, Dean PN, Dressler LG, Rabinovitch PS, Stewart CV, Tanke HJ, Wheeless LL . 1988 Current Protocols in Cytometry pp 7.4.1ā7.4.8 John Wiley and Sons
Rouvier E, Luciani MF, Golstein P . 1993 J. Exp. Med. 177: 195ā20
Soussi T, Caron de Fromentel C, Breugnot C, May E . 1988 Nucleic Acids Res. 16: 11384ā
Sreedhar AS, Pardhasaradhi BVV, Begum Z, Khar A, Srinivas UK . 1999 FEBS Lett. 456: 339ā342
Sreedhar AS, Pardhasaradhi BVV, Khar A, Srinivas UK . 2000 FEBS Lett. 472: 271ā275
Swamynathan SK, Revathi CJ, Srinivas UK . 1996 DNA Cell Biol. 15: 897ā905
Towbin H, Stachelin T, Gordon J . 1979 Proc. Natl. Acad. Sci. USA 76: 4350ā4354
Trauth BC, Klas C, Peters AM, Matzku S, Moller P, Falk W, Debatin KM, Krammer PH . 1989 Science 245: 539ā542
Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S . 1992 Nature 356: 314ā317
Wyllie AH, Kerr JF, Curie AR . 1980 Int. Rev. Cytol. 68: 251ā306
Zhou B-B, Li H, Yuan J, Kirschner MW . 1998b Proc. Natl. Acad. Sci. USA 95: 6785ā6790
Zhou M, Gu L, Yeager AM, Findley HW . 1998a Leukemia 12: 1756ā1763
Acknowledgements
Authors wish to thank Mr K Kennady for helping us with flow cytometry and Mr MV Subbarao for secretarial assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sreedhar, A., Pardhasaradhi, B., Khar, A. et al. Effect of C-terminal deletion of P53 on heat induced CD95 expression and apoptosis in a rat histiocytoma. Oncogene 21, 4042ā4049 (2002). https://doi.org/10.1038/sj.onc.1205504
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1205504