Prion Protein (p. 486)
Collinge J. (2001) Prion diseases of humans and animals: their causes and molecular basis. Annu. Rev. Neurosci. 24: 519-550
Dobson C.M. (2002) Protein-misfolding diseases: Getting out of shape. Nature 418: 729-730
Hinchcliffe E.H. and Sluder G. (2001) "It takes two to tango": understanding how centrosome duplication is regulated throughout the cell cycle. Genes & Devel. 15: 1167-1181
Prusiner S.B. (2004) Detecting mad cow disease. Scientific American July 2004: 86-93
Roth M.G. (1999) Inheriting the Golgi. Cell: 559-562
Stearns T. (2001) Centrosome duplication: A centriolar pas de deux. Cell 105: 417-420
Castilla J, Saa P, Hetz C, Soto C. (2005) In vitro generation of infectious scrapie prions. Cell 121: 195-206
The authors show that the conversion of normal cellular prion protein (PrPC) into protein-resistent prion protein (PrPres) can be mimicked in vitro by cyclic amplification of protein misfolding, resulting in indefinite amplification of PrPres. The in vitro-generated forms of PrPres share similar biochemical and structural properties with PrPres derived from sick brains. Inoculation of wild-type hamsters with in vitro-produced PrPres led to a scrapie disease identical to the illness produced by brain infectious material. These findings demonstrate that prions can be generated in vitro and provide strong evidence in support of the protein-only hypothesis of prion transmission.
Legname G, Baskakov IV, Nguyen HO, Riesner D, Cohen FE, DeArmond SJ, Prusiner SB. (2004) Synthetic mammalian prions. Science 305: 673-676.
Recombinant mouse prion protein (recMoPrP) produced in Escherichia coli was polymerized into amyloid fibrils that represent a subset of beta sheet-rich structures. Fibrils consisting of recMoPrP(89-230) were inoculated intracerebrally into transgenic (Tg) mice expressing MoPrP(89-231). The mice developed neurologic dysfunction between 380 and 660 days after inoculation. Brain extracts showed protease-resistant PrP by Western blotting; these extracts transmitted disease to wild-type FVB mice and Tg mice overexpressing PrP, with incubation times of 150 and 90 days, respectively. Neuropathological findings suggest that a novel prion strain was created. Our results provide compelling evidence that prions are infectious proteins.
Mead S. et al. (2003) Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemics. Science 300: 640-643
O'Connell K.F., Caron C., Kopish K.R., Hurd
D.D., Kemphues K.J., Li Y. and White J.G. (2001) The C.
elegans zyg-1 gene encodes a regulator of centrosome
duplication with with distinct maternal and paternal roles in the
embryo. Cell 105: 547-558
The authors investigate the control of centrosome duplication during the cell cycle. The zyg-1+ gene encodes a protein kinase that is specifically required for daughter centriole formation. Loss-of-function mutants form monopolar mitotic spindles organized by a single centrosome. Zyg-1 protein localizes transiently to centrosomes and acts at least one cell cycle prior to each spindle assembly event. Paternal zyg-1 protein is required during the first cell cycle and maternal zyg-1 thereafter.
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