Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Reexamination Certificate
1999-02-12
2001-09-11
Krass, Frederick (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
C514S278000, C435S962000, C435S159000, C435S173300, C435S174000, C436S063000, C436S071000, C436S086000, C436S087000, C436S092000
Reexamination Certificate
active
06288048
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates generally to the field of protein processing and protein signalling pathways and specifically to two novel proteins having distinct activities, which are derived from a common hedgehog protein precursor.
2. Related Art
Over the past decade, extracellular protein signals encoded by several gene families have emerged as central players in coordinating cell behavior and thus generating pattern during animal development. Members of the hedgehog (hh) gene family in particular are notable for their association with several well-studied patterning activities. In Drosophila, where hh was discovered and isolated, patterning functions include specification of positional identity within developing segments and appendages. In vertebrate embryos, function of the hh family member Sonic hedgehog (Shh) is associated with the patterning influences of notochord and prechordal plate mesoderm on spinal cord and brain, as well as on other surrounding structures. Shh expressed in mesoderm at the posterior margin of the developing vertebrate limb bud also plays a central role in controlling limb outgrowth and patterning. The patterning functions of hh proteins have been extensively studied (see Hammerschmidt et al. 1997 for a recent general review), and novel functions continue to emerge.
SUMMARY OF THE INVENTION
This article presents a selective view of the hh protein biogenesis and signaling pathways, with particular attention paid to the involvement of the abundant neutral lipid cholesterol. One role for cholesterol is as a covalent adduct for the biologically active form of the hh protein (Hh), which is formed as a product of an autoprocessing reaction that entails internal cleavage. Cholesterol attachment restricts the spatial deployment of the Hh signal, thus influencing the pattern of cellular responses in developing tissues. Here we summarize our studies of the Hh autoprocessing reaction, and of the role of cholesterol in this reaction. We also summarize more recent studies suggesting that, in addition to its role in Hh signal production, cholesterol has an essential role in mediating the response to the Hh signal within target cells. This role is revealed by genetic or drug-induced perturbations of cholesterol homeostasis that render target tissues unresponsive to the Hh signal.
In yet another embodiment, the invention provides a method for identifying a compound which affects hedgehog activity comprising incubating the compound with hedgehog polypeptide, or with biologically active fragments thereof, or with a recombinant cell expressing hedgehog, under conditions sufficient to allow the components to interact; and determining the effect of the compound on hedgehog activity or expression. For example, cholesterol level (e.g., biosynthesis or transport) is measured as an inidicator of hedgehog activity. In one aspect of the invention, the method provides a means for affecting cholesterol biosynthesis or transport in a cell comprising contacting a cell with an effective amount of a compound that affects hedgehog, thereby affecting cholesterol biosynthesis or transport. The effect may be inhibition or stimulation of cholesterol biosynthesis or transport.
REFERENCES:
patent: 5789543 (1998-09-01), Ingham et al.
patent: 5844079 (1998-12-01), Ingham et al.
Porter et al, Science, vol. 274, pp. 255-259, “Cholesterol Modification of Hedgehog Signaling Proteins in Animal Development”, Oct. 1986.*
Campbell et al, Tetralogy, vol. 36, pp. 235-243, “Comparative Effects of Retinoic Acid and Jervine on Chondrocyte Differentiation”, Mar. 1987.*
Keeler, Proceedings of the Society for Experimental Biology and Medicine, vol. 149, pp. 302-306, “Teratogenic Effects of Cyclopamine and Jervine in Rats, Mice and Hamsters”, May 1975.
Beachy Philip A.
Cooper Michael K.
Porter Jeffrey A.
Gray Cary Ware & Freidenrich LLP
Haile Lisa A.
Krass Frederick
The Johns Hopkins University School of Medicine
LandOfFree
Cholesterol and hedgehog signaling does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Cholesterol and hedgehog signaling, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Cholesterol and hedgehog signaling will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2548830