Fbxl3 binds phosphorylated Cry proteins

Stable Identifier
R-MMU-508640
Type
Reaction [binding]
Species
Mus musculus
Compartment
nucleoplasm
ReviewStatus
5/5
General
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Fbxl3 binds phosphorylated Cry proteins
Fbxl3 is an F-box type component of a particular SKP/CUL/F-Box E3 ubiquitin ligase. Fbxl3 interacts specifically with Cry1 and Cry2 in the cytosol to direct the polyubiquitination of Cry1 and Cry2. Polyubiquitination of Cry proteins directs them to the 26S proteasome for degradation.
It is unknown if Fbxl3 requires phosphorylation or other modification of Cry proteins in order to bind and ubiquitinate them. Phosphorylation of Cry by Adenosine monophosphate-dependent kinase increases the degradation of Cry, apparently by increasing interaction of Cry with Fbxl3. The reaction depicted here shows phosphorylated Cry because LRR domains, such as that of Fbxl3, bind phosphorylated residues. The location of the reaction is also unknown. The reaction is depicted in the nucleoplasm because Fbxl3 is predominantly nuclear.
Literature References
PubMed ID Title Journal Year
17463252 The after-hours mutant reveals a role for Fbxl3 in determining mammalian circadian period

Lalanne, Z, Shaw, L, Hastings, MH, Tucci, V, Pagano, M, Barnard, AR, Nolan, PM, Brooker, D, O'neill, J, Chesham, JE, Kendall, R, Busino, L, Quwailid, MM, Maywood, ES, Godinho, SI, Romero, MR

Science 2007
17463251 SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins

Maiolica, A, Busino, L, Draetta, GF, Bassermann, F, Godinho, SI, Lee, C, Pagano, M, Nolan, PM

Science 2007
17462724 Circadian mutant Overtime reveals F-box protein FBXL3 regulation of cryptochrome and period gene expression

Siepka, SM, Song, W, Hu, Y, Yoo, SH, Lee, C, Park, J, Takahashi, JS, Kumar, V

Cell 2007
19833968 AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation

Juguilon, H, Panda, S, Alvarez, JG, Evans, RM, Shaw, RJ, Vasquez, DS, Williams, EC, Lamia, KA, Thompson, CB, Egan, DF, DiTacchio, L, Sachdeva, UM

Science 2009
Participants
Input
Output
Orthologous Events
FBXL3 binds phosphorylated CRY proteins (Homo sapiens)
Authored
May, B  (2010-02-20)
Reviewed
Delaunay, F  (2010-06-23)
Kay, SA  (2010-06-23)
Hirota, T  (2010-06-23)
Albrecht, U  (2010-06-23)
Created
May, B  (2010-02-16)
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