Programmed cell death (PCD) is a fundamental process that is recognized to occur in eukaryotes and prokaryotes. During development of a multicellular organism, certain cells are destined to turnover in relatively predictable times and places. In addition, environmental and hormonal signals can also activate a cellular suicide program.
Although PCD has been intensely studied in the past decade, particularly in mammalian cells and C. elegans, the actual mechanism through which eukaryotic cells commit suicide remains enigmatic. The current working hypothesis in this field is that the cellular machinery for PCD is present all the time in eukaryotic cells and is actively suppressed by certain proteins. This exciting finding suggests that the underlying mechanism for PCD may be conserved across plant and animal kingdoms.
Our aim is to further the understanding of the regulation of PCD in plants at the molecular and biochemical levels. To this end, we have been studying to ascertain functional roles of evolutionary conserved proteins, metacaspases (MCPs) and Bax inhibitor-1 (BI-1), in the regulation of plant PCD and its related stress signaling/response. For such research, we use the model organisms such as Arabidopsis thaliana and Nicotiana tabacum, and a combinational technique of molecular genetics, biochemistry, cell biology and post-genomic tools.
Publications related to this project:
39.Watanabe N, and Lam E. Arabidopsis Metacaspase 2d Is a Positive Mediator of Cell Death Induced during Biotic and Abiotic Stresses. Plant J. [Epub ahead of print]. [Pubmed]
37. Watanabe N, and Lam E. Calcium-dependent activation and autolysis of Arabidopsis metacaspase 2d. J. Biol. Chem. 2011. Jan 6. [Epub ahead of print].
36. Watanabe, N., and Lam, E. (2009) Bax Inhibitor-1, a conserved plant cell death suppressor, is a key switch downstream from a variety of biotic and abiotic stress signals. Int. J. Mol. Sci. (10(7), 3149-3167.
35. Watanabe, N., and Lam, E. (2009) "Programmed Cell Death in Plant Biology". In Essentials of Apoptosis: A Guide for Basic and Clinical Research. Eds. Yin X.Y, and Dong Z. Humana Press. p301-p324.
34. Lam, E. (2008) “Programmed Cell Death In Plants: Orchestrating an Intrinsic Suicide Program Within Walls.” Critical Rev. Plant Sci. 27(6): 413-423.
33. Watanabe, N., and Lam, E. (2008) "Arabidopsis Bax Inhibitor-1: a Rheostat for ER Stress-induced Programmed Cell Death." Plant Signaling & Behavior 3(8): 564-566.
32. Watanabe, N., and Lam, E. (2008) "BAX Inhibitor-1 modulates endoplasmic reticulum stress-mediated programmed cell death in Arabidopsis" J. Biol. Chem. 283(6): 3200-3210.
31. Qutob, D., Kemmerling, B., Brunner, F., Küfner, I., Engelhardt, S., Gust, A., Luberacki, Seitz, U.-H., Stahl, D., Rauhut, T., Glawischnig, E., Schweene, G., Lacombe, B., Watanabe, N., Lam, E., Schlichting, R., Scheel, D., Nau, K., Dodt, G., Hubert, G., Gijzen, M., Nürnberger, T. (2006) Phytotoxicity and innate immune responses induced by Nep1-like proteins. Plant Cell 18(12): 3721-3744.
30. Watanabe, N, Lam, E. (2006) Arabidopsis Bax Inhibitor-1 functions as an attenuator of biotic and abiotic types of cell death. Plant Journal 45(6):884-894.
29. Rosin FM., Watanabe N, Lam E. (2005) Moonlighting vacuolar protease: jobs for a busy protein. Trends in Plant Sci. 10(11):516-518.
28. Watanabe N, and Lam E. (2005) Two Arabidopsis metacaspases, AtMCP1b and AtMCP2b, are arginine/lysine-specific cysteine proteases and activate apoptosis-like cell death in yeast. J. Biol. Chem. 280(15): 14691-14699.
27. Lam E. (2005) Vacuolar proteases liveining up programmed cell death. Trends in Cell Biol. 15(3): 124-127.
26. Watanabe N, Lam E. (2005) The hypersensitive response in plant disease resistance. Multigenic and Induced Systemic Resistance in Plants. p83-p111. Tuzen E. & Bent E. Eds. Springer
25. Watanabe N, and Lam E. (2004) Recent advance in the study of caspase-like proteases and Bax-inhibitor 1: their possible role as regulator of programmed cell death in plants. Mol. Plant Pathol. 5(1): 65-70.
24. Lam E. (2004) Controlled cell death, plant survival and development. Nature Rev. Mol. Cell. Biol. 5(4): 305-315.
23. del Pozo O, and Lam E. (2003) Expression of the baculovirus p35 protein in tobacco delays cell death progression and compromise N gene-mediated disease resistance response to tobacco mosaic virus. Mol. Plant-Microbe Interact. 16(6): 485-494.
22. Pontier D, del Pozo O and Lam E. (2003) Cell death in plant disease: mechanisms and molecular markers. Chapter in "Plant Cell Death Processes". Nooden LA Ed, p37-p50. Elsevier Academic Press.
21. Pontier D, Mittler R, and Lam E. (2002) Mechanism of cell death and disease resistance induction by transgenic expression of bacterio-opsin. Plant J. 30(5): 499-509.
20. Lam E, Kato N, and Lawton M. (2001) Programmed cell death, mitochondria and the plant hypersentive response. Nature 411(6839): 848-853.
19. Pontier D, Miao ZH, and Lam E. (2001) Specific trans-dominant suppression of plant TGA factors reveals complex regulatory functions in plant defense reponses. Plant J. 27(6): 529-538.
18. Zhou JM, Trifa Y, Silva H, Pontier D, Lam E, Shah J, and Klessig DF. (2000) NPR1 differentially interacts with members of the TGA/OBF family of transcription factors that bind an element of the PR-1 gene required for induction by salicylic acid. Mol. Plant-Microbe Interact. 13(2):191-202.
17. Lam E, and del Pozo O. (2000) Caspase-like protease involvement in the control of plant cell death. Plant Mol Biol. 44(3): 417-428.
16. Lam E, and Greenberg J. (2000) Cell death: the 'Yin' path in the balancing act of the life cycle. Plant Mol Biol. 44(3): vii-viii.
15. Mittler R, Lam E, Shulaev V, and Cohen M. (1999) Signals controlling the expression of cytosolic ascorbate peroxidase during pathogen-induced programmed cell death in tobacco. Plant Mol. Biol. 39(5): 1025-1035.
14. Lam E, Pontier D, and del Pozo O. (1999) Die and let live - programmed cell death in plants. Curr. Opin. Plant Biol. 2(6): 502-507.
13. Pontier D, Gan S, Amasino RM, Roby D, and Lam E. (1999) Markers for hypersensitive response and senescence show distinct patterns of expression. Plant Mol. Biol. 39(6):1243-1255.
12. Lam E, del Pozo O, and Pontier D. (1999) BAXing in the hypersensitive response. Trends Plant Sci. 4(11): 419-421.
11. del Pozo O, and Lam E. (1998) Caspases and programmed cell death in the hypersensitive response of plants to pathogens. Curr. Biol. 8(20):1129-1132.
10. Pontier D, Tronchet M, Rogowski P, Lam E, and Roby D. (1998) Activation of hsr203, a plant gene expressed during incompatible plant-pathogen interactions, is correlated with programmed cell death. Mol. Plant-Microbe Interact. 11: 544-554.
9. Mittler R, del Pozo O, Meisel L, and Lam E. (1997) Pathogen-induced programmed cell death in plants, a possible defense mechanism. Dev. Genet. 21(4) :279-289.
8. Mittler R, Simon L, and Lam E. (1997) Pathogen-induced programmed cell death in tobacco. J. Cell Sci. 110(11): 1333-1344.
7. Mittler R, and Lam E. (1997) Characterization of nuclease activities and DNA fragmentation induced upon hypersensitive response cell death and mechanical stress. Plant Mol. Biol. 34(2): 209-221.
6. Abad MS, Hakimi SM, Kaniewski WK, Rommens CMT, Shulaev V, Lam E, and Shah DM. (1997) Characterization of acquired resistance in lesion-mimic transgenic potato expressing bacterio-opsin. Mol Plant-Microbe Interact. 10(5): 635-645.
5. Mittler R, Shulaev V, Seskar M, and Lam E. (1996) Inhibition of programmed cell death in tobacco plants during a pathogen-induced hypersensitive response at low oxygen pressure. Plant Cell 8(11): 1991-2001
4. Mittler R, and Lam E. (1996) Sacrifice in the face of foes: pathogen-induced programmed cell death in plants. Trends in Microbiol. 4(1): 10-15.
3. Mittler R, and Lam E. (1995) Identification, characterization, and purification of a tobacco endonuclease activity induced upon hypersensitive response cell death. Plant Cell 7(11): 1951-1562.
2. Mitter R, Shulaev V, and Lam E. (1995) Coordinated activation of programmed cell death and defence mechanisms in transgenic tobacco plants expressing a bacterial proton pump. Plant Cell 7(1): 29-42.
1. Mittler R, and Lam E. (1995) In situ detection of nDNA fragmentation during the differentiation of trachearry elements in higher plants. Plant Physiol. 108: 489-493.