Dimerization of CUL7 and PARC is not required for all CUL7 functions and mouse development.
CUL7, a recently identified member of the cullin family of E3 ubiquitin ligases, forms a unique SCF-like complex and is required for mouse embryonic development. To further investigate CUL7 function, we sought to identify CUL7 binding proteins. The p53-associated, parkin-like cytoplasmic protein (PARC), a homolog of CUL7, was identified as a CUL7-interacting protein by mass spectrometry. The heterodimerization of PARC and CUL7, as well as homodimerization of PARC and CUL7, was confirmed in vivo. To determine the biological role of PARC by itself and in conjunction with CUL7, a targeted deletion of Parc was created in the mouse. In contrast to the neonatal lethality of the Cul7 knockout mice, Parc knockout mice were born at the expected Mendelian ratios and exhibited no apparent phenotype. Additionally, Parc deletion did not appear to affect the stability or function of p53. These results suggest that PARC and CUL7 form an endogenous complex and that PARC and CUL7 functions are at least partially nonoverlapping. In addition, although PARC and p53 form a complex, the absence of effect of Parc deletion on p53 stability, localization, and function suggests that p53 binding to PARC may serve to control PARC function.
Skaar
Jeffrey R
JR
Dana-Farber Cancer Institute, Department of Medical Oncology and Harvard Medical School, Mayer Building 457, 44 Binney Street, Boston, Massachusetts 02115, USA.
Arai
Takehiro
T
DeCaprio
James A
JA
D000818:Animals; D051023:BH3 Interacting Domain Death Agonist Protein; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D027101:DNA Topoisomerase IV / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D004622:Embryo, Mammalian; D047108:Embryonic Development; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D051379:Mice; D018345:Mice, Knockout; D011233:Precipitin Tests; D011485:Protein Binding; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D051023:BH3 Interacting Domain Death Agonist Protein; C494815:Bid protein, mouse; D002352:Carrier Proteins; D016159:Tumor Suppressor Protein p53; D027101:DNA Topoisomerase IV