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Biotech / Medical : T/FIF, a New Plateau -- Ignore unavailable to you. Want to Upgrade?

To: tom pope who wrote (828)	1/25/2002 8:17:00 PM
From: tom pope	Respond to of 2243

oops, now see that my immediately preceding is open to misinterpretation. I meant to say I didn't buy ONXX, not that I was smart enough to short it in the 20's, sadly.

To: tom pope who wrote (828)	1/25/2002 8:23:27 PM
From: scaram(o)uche	Respond to of 2243

20s? Ouch. I hope you're implying that you DID short it. Eyeballing cash in the bank and recent purchases that I have not added in..... we have about $18K left to mobilize. There have been giant bails. Anything on anybody's radar? Tuck..... ubiquitin ligases..... a wee bit of relevance...... J Cell Biol 2002 Jan 21;156(2):249-60 The checkpoint protein Chfr is a ligase that ubiquitinates Plk1 and inhibits Cdc2 at the G2 to M transition. Kang D, Chen J, Wong J, Fang G. Department of Biological Sciences, Stanford University, Stanford, CA 94305. The checkpoint protein Chfr delays entry into mitosis, in the presence of mitotic stress (Scolnick, D.M., and T.D. Halazonetis. 2000. Nature. 406:430-435). We show here that Chfr is a ubiquitin ligase, both in vitro and in vivo. When transfected into HEK293T cells, Myc-Chfr promotes the formation of high molecular weight ubiquitin conjugates. The ring finger domain in Chfr is required for the ligase activity; this domain auto-ubiquitinates, and mutations of conserved residues in this domain abolish the ligase activity. Using Xenopus cell-free extracts, we demonstrated that Chfr delays the entry into mitosis by negatively regulating the activation of the Cdc2 kinase at the G2-M transition. Specifically, the Chfr pathway prolongs the phosphorylated state of tyrosine 15 in Cdc2. The Chfr-mediated cell cycle delay requires ubiquitin-dependent protein degradation, because inactivating mutations in Chfr, interference with poly-ubiquitination, and inhibition of proteasomes all abolish this delay in mitotic entry. The direct target of the Chfr pathway is Polo-like kinase 1 (Plk1). Ubiquitination of Plk1 by Chfr delays the activation of the Cdc25C phosphatase and the inactivation of the Wee1 kinase, leading to a delay in Cdc2 activation. Thus, the Chfr pathway represents a novel checkpoint pathway that regulates the entry into mitosis by ubiquitin-dependent proteolysis.