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Growth suppression by Lkb1 is mediated by a G 1 cell cycle arrest
Open accessAbstract
Germ-line mutations of LKB1 ( STK11 ) lead to Peutz–Jeghers syndrome characterized by gastrointestinal polyps and cancer of different organ systems. The mutations lead to loss or severe impairment of Lkb1 serine/threonine kinase activity. Therefore LKB1 has been implicated as a tumor suppressor gene, but only a few mutations in the coding exons of LKB1 have been detected in sporadic tumors. Here, we have identified tumor cell lines with severely reduced mRNA levels and impaired Lkb1 kinase activity. Reintroducing Lkb1 into these cells suppressed cell growth. The Lkb1-mediated growth inhibition was caused by a G 1 cell cycle block and was not detected with several naturally occurring Lkb1 mutants. These results indicate that LKB1 has functional and specific growth-suppressing activity.
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Cited by
Shaw, R. J., Kosmatka, M., Bardeesy, N., Hurley, R. L., Witters, L. A., DePinho, R. A., & Cantley, L. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308061100 · Cited by 1,797
LKB1 is the upstream kinase in the AMP-activated protein kinase cascade
Woods, A., Johnstone, S. R., Dickerson, K., Leiper, F. C., Fryer, L. G. D., Neumann, D., Schlattner, U., Wallimann, T., Carlson, M., & Carling, D. (2003) · Current Biology · doi:10.1016/j.cub.2003.10.031 · Cited by 1,650
Hawley, S. A., Pan, D. A., Mustard, K. J., Ross, L., Bain, J., Edelman, A. M., Frenguelli, B. G., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.009 · Cited by 1,589
Brugarolas, J., Lei, K., Hurley, R. L., Manning, B. D., Reiling, J. H., Hafen, E., Witters, L. A., Ellisen, L. W., & Kaelin, W. G. (2004) · Genes & Development · doi:10.1101/gad.1256804 · Cited by 1,384
LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR‐1
Lizcano, J. M., Göransson, O., Toth, R., Deak, M., Morrice, N. A., Boudeau, J., Hawley, S. A., Udd, L., Mäkelä, T. P., Hardie, D. G., et al. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600110 · Cited by 1,381
Self-citationAMP-activated Protein Kinase and the Regulation of Autophagic Proteolysis
Meley, D., Bauvy, C., Houben-Weerts, J. H. P. M., Dubbelhuis, P. F., Helmond, M. T. J., Codogno, P., & Meijer, A. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605488200 · Cited by 419
Epigenetic control of rDNA loci in response to intracellular energy status
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Xie, Z., Dong, Y., Scholz, R., Neumann, D., & Zou, M.-H. (2008) · Circulation · doi:10.1161/circulationaha.107.744490 · Cited by 273
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Morton, J. P., Jamieson, N. B., Karim, S. A., Athineos, D., Ridgway, R. A., Nixon, C., McKay, C. J., Carter, R., Brunton, V. G., Frame, M. C., et al. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.04.055 · Cited by 169
Lysosomal recruitment of TSC2 is a universal response to cellular stress
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Pérez-Revuelta, B. I., Hettich, M. M., Ciociaro, A., Rotermund, C., Kahle, P. J., Krauss, S., & Di Monte, D. A. (2014) · Cell Death & Disease · doi:10.1038/cddis.2014.175 · Cited by 140
An improved platform for functional assessment of large protein libraries in mammalian cells
Matreyek, K. A., Stephany, J. J., Chiasson, M. A., Hasle, N., & Fowler, D. M. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz910 · Cited by 122
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“HeLa-S3 cells contain undetectable levels of endogenous LKB1 [3].”
Background
Metadata
- Authors
- Tiainen, M., Ylikorkala, A., & Mäkelä, T. P.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1999-08-03
- Volume
- 96
- Issue
- 16
- Pages
- 9248-9251
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2132708041
- Cited by
- 301
- References
- 0
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- green
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