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J. Biol. Chem., Vol. 281, Issue 36, 26725-26733, September 8, 2006

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CDMP1/GDF5 Has Specific Processing Requirements That Restrict Its Action to Joint Surfaces^*

From the Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Bethesda, Maryland 20892

CDMP1/GDF5 has not demonstrated biological activity in Xenopus embryos when overexpressed by mRNA injection. We provide biological and biochemical evidence that to become active, the protein requires cleavage by two distinct proteolytic enzymes. We demonstrate a specific overlap in the expression patterns of CDMP1/GDF5 with the proteases required to release the mature peptide at the location of the future articular surface but not in the future joint space. Taken together, these observations provide a plausible mechanism for local action of CDMP1/GDF5 consistent with requirements imposed by current models of pattern formation in the developing limb.

Received for publication, April 21, 2006

The nucleotide sequence(s) reported in this paper has been submitted to Gen-Bank^TM EBI Data Bank with the accession number(s) AY685227 [GenBank] and AY685228 [GenBank] .

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1-3.

¹ To whom correspondence may be addressed. E-mail: john.thomas{at}fda.hhs.gov.

² To whom correspondence may be addressed. E-mail: malcolm.moos{at}fda.hhs.gov.

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