Reactome | Degradation of CRY and PER proteins

Degradation of CRY and PER proteins

Stable Identifier

R-HSA-9932298

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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In order to initiate a new round of transcription activated by BMAL1:CLOCK in the morning, Cryptochrome proteins (CRY1, CRY2) and Period proteins (PER1, PER2, PER3), the repressors of BMAL:CLOCK, are ubiquitinylated by SCF E3 ligase complexes and then proteolyzed by the 26S proteasome during the night. The BTRC,FBXW11:CUL1:SKP1:RBX1 E3 ligase complex ubiquitinylates phosphorylated PER1, PER2, and likely PER3 in the cytosol (Shirogane et al. 2005, inferred from mouse homologs in Reischl et al. 2007, Ohsaki et al. 2008), the FBXL3:CUL1:SKP1:RBX1 E3 ligase complex ubiquitinylates CRY1 and CRY2 in the nucleoplasm (inferred from mouse homologs in Busino et al. 2007, Hirano et al. 2013, Yoo et al. 2013), and the FBXL21:CUL1:SKP1:RBX1 E3 ligase complex ubiquitinylates CRY1 and CRY2 in the cytosol (inferred from mouse homologs in Hirano et al. 2013, Yoo et al. 2013). FBLX21 represses ubiquitinylation by FBXL3 in the nucleus by an uncharacterized mechanism (inferred from mouse homologs in Hirano et al. 2013, Yoo et al. 2013)

Literature References

PubMed ID	Title	Journal	Year
15917222	SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein Shirogane, T, Jin, J, Ang, XL, Harper, JW	J Biol Chem	2005
23452856	FBXL21 regulates oscillation of the circadian clock through ubiquitination and stabilization of cryptochromes Hirano, A, Yumimoto, K, Tsunematsu, R, Matsumoto, M, Oyama, M, Kozuka-Hata, H, Nakagawa, T, Lanjakornsiripan, D, Nakayama, KI, Fukada, Y	Cell	2013
18782782	The role of {beta}-TrCP1 and {beta}-TrCP2 in circadian rhythm generation by mediating degradation of clock protein PER2 Ohsaki, K, Oishi, K, Kozono, Y, Nakayama, K, Nakayama, KI, Ishida, N	J Biochem	2008
17463251	SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins Busino, L, Bassermann, F, Maiolica, A, Lee, C, Nolan, PM, Godinho, SI, Draetta, GF, Pagano, M	Science	2007
23452855	Competing E3 ubiquitin ligases govern circadian periodicity by degradation of CRY in nucleus and cytoplasm Yoo, SH, Mohawk, JA, Siepka, SM, Shan, Y, Huh, SK, Hong, HK, Kornblum, I, Kumar, V, Koike, N, Xu, M, Nussbaum, J, Liu, X, Chen, Z, Chen, ZJ, Green, CB, Takahashi, JS	Cell	2013