This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Skaar, J. R. Articles by DeCaprio, J. A. Search for Related Content PubMed PubMed Citation Articles by Skaar, J. R. Articles by DeCaprio, J. A.

PARC and CUL7 Form Atypical Cullin RING Ligase Complexes

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, ² Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, and ³ The Stowers Institute for Medical Research, Kansas City, Missouri

Requests for reprints: James A. DeCaprio, Dana-Farber Cancer Institute, Mayer 440, 44 Binney Street, Boston, MA 02115. Phone: 617-632-3825; Fax: 617-582-8601; E-mail: james_decaprio{at}dfci.harvard.edu.

CUL7 and the p53-associated, PARkin-like cytoplasmic protein (PARC) were previously reported to form homodimers and heterodimers, the first demonstration of cullin dimerization. Although a CUL7-based SKP1/CUL1/F-box (SCF)–like complex has been observed, little is known about the existence of a PARC-based SCF-like complex and how PARC interacts with CUL7-based complexes. To further characterize PARC-containing complexes, we examined the ability of PARC to form an SCF-like complex. PARC binds RBX1 and is covalently modified by NEDD8, defining PARC as a true cullin. However, PARC fails to bind SKP1 or F-box proteins, including the CUL7-associated FBXW8. To examine the assembly of PARC- and CUL7-containing complexes, tandem affinity purification followed by multidimensional protein identification technology were used. Multidimensional protein identification technology analysis revealed that the CUL7 interaction with FBXW8 was mutually exclusive of CUL7 binding to PARC or p53. Notably, although heterodimers of CUL7 and PARC bind p53, p53 is not required for the dimerization of CUL7 and PARC. The observed physical separation of FBXW8 and PARC is supported functionally by the generation of Parc–/–, Fbxw8–/– mice, which do not show exacerbation of the Fbxw8–/– phenotype. Finally, all of the PARC and CUL7 subcomplexes examined exhibit E3 ubiquitin ligase activity in vitro. Together, these findings indicate that the intricate assembly of PARC- and CUL7-containing complexes is highly regulated, and multiple subcomplexes may exhibit ubiquitin ligase activity. [Cancer Res 2007;67(5):2006–14]

This article has been cited by other articles:

				J. R. Skaar, D. J. Richard, A. Saraf, A. Toschi, E. Bolderson, L. Florens, M. P. Washburn, K. K. Khanna, and M. Pagano INTS3 controls the hSSB1-mediated DNA damage response J. Cell Biol., October 5, 2009; 187(1): 25 - 32. [Abstract] [Full Text] [PDF]

				T. Tsutsumi, H. Kuwabara, T. Arai, Y. Xiao, and J. A. DeCaprio Disruption of the Fbxw8 Gene Results in Pre- and Postnatal Growth Retardation in Mice Mol. Cell. Biol., January 15, 2008; 28(2): 743 - 751. [Abstract] [Full Text] [PDF]