Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1994-10-19
1997-08-12
Allen, Marianne P.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
536 235, 530350, 435 691, C12N 1512, A61K 3817, C07K 14435
Patent
active
056565950
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to novel peptide and nucleotide sequences, and to their pharmaceutical use. More especially, the invention relates to peptides capable of modulating the levels of GDP exchange with p21-GDP complexes.
The products of ras genes, generally designated p21 proteins, perform a key role in the control of cell division in all eukaryotic organisms in which they have been investigated. Some specific modifications of these proteins cause them to lose their normal control and lead them to become oncogenic. Thus, a large number of human tumours have been associated with the presence of modified ras genes. Similarly, an overexpression of these p21 proteins can lead to a disturbance of cell proliferation. An understanding of the exact role of these p21 proteins in cells, their mode of functioning and their characteristics hence constitutes a major stake for an understanding of and therapeutic approach to carcinogenesis.
In vivo, the exact nature of the events responsible for the activation of p21 proteins is not yet known. It is known that they exert their functions by fluctuating between two confirmational states; an inactive form bound to GDP and an active form bound to GTP, but the factors effecting the transition between these two forms are not clearly identified. Recent studies report physiological situations during which the proportion of ras proteins bound to GTP increases in the cell. These situations comprise the activation of T lymphocytes and the stimulation of 3T3 fibroblasts by growth factors including EGF and PDGF (Downward et al., Nature 346 (1990) 719; Gibbs et al., J. Biol. Chem. 265 (1990) 20437). The increase in the proportion of p21-GTP may be at least partially explained by the action of a protein performing a role analogous to that of a receptor of the G proteins of transduction. In this connection, some proteins capable of promoting the exchange of GDP with p21 proteins have been identified, from ox brain [West et al., FEBS Lett. 259 (1990) 245] and rat brain [Wolfman and Macara, Science 248 (1990) 67]. The differing cellular localization of these under which they were obtained suggests that they are different proteins. They are as active on normal ras proteins as on those which are oncogenic. These activities are grouped together under the term GEF: Guanidine nucleotide Exchange Factor, or GRF.
In Saccharomyces cerevisiae yeast, GRF activity has been attributed to the product of the CDC25 gene [Camonis et al., EMBO J. 5 (1986) 375], and studies have been carried out in order to understand the signalling pathway involving the product of the CDC25, RAS1 and RAS2 genes on the one hand and adenylate cyclase on the other hand in Saccharomyces cerevisiae yeast. In particular, many studies have focused on characterization of the product of the CDC25 gene, which was the least known element of this chain. The product of the CDC25 gene constitutes the element furthest upstream in the cascade of reactions leading to the activation of p21 in yeast. The work carried out in this field has contributed to demonstrating that the product of this gene must act as a GDP.fwdarw.GTP exchange factor for activating ras proteins. A second gene of S. cerevisiae yeast, SDC25, structurally very closely related to CDC25, has been isolated and characterized. The active domain of SDC25 seems to be an exchange factor capable of acting in vitro and in vivo on ras proteins. This domain constitutes the first molecular constituent described which is endowed with this activity.
Very recently, a protein of the GRF type has also been demonstrated in mice [Vanoni and Martegani, J. Cell. Bioch. Suppl. 16B (1992) 220].
However, to date, no GRF activity has been isolated and characterized in man. The present invention is specifically the outcome of the demonstration by the Applicant of the existence of a human GDP exchange factor. The present invention is, more especially, the outcome of the identification, isolation and characterization of peptides and nucleotide sequences of human origin, designated hGRF and
REFERENCES:
Bonfini, L. et al., Science, 255: 603-606, 1992 (Jan.).
Shou et al., Nature, 358: 351-4, 1992 (Jul.).
Martegani, E, et al., EMBO J., 11(6): 2151-7, 1992 (Jun.).
Wei, W. et al., PNAS, 89: 7100-7104, Aug. 1992.
Schweighoffer Fabien
Tocque Bruno
Allen Marianne P.
Rhone-Poulenc Rorer S.A.
Savitzky Martin F.
Smith Julie K.
LandOfFree
Peptides having GDP exchange factor activity, nucleic acid seque does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Peptides having GDP exchange factor activity, nucleic acid seque, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Peptides having GDP exchange factor activity, nucleic acid seque will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-160487