Atlas on substrate recognition subunits of CRL2 E3 ligases.
The Cullin2-type ubiquitin ligases belong to the Cullin-Ring Ligase (CRL) family, which is a crucial determinant of proteasome-based degradation processes in eukaryotes. Because of the finding of von Hippel-Lindau tumor suppressor (VHL), the Cullin2-type ubiquitin ligases gain focusing in the research of many diseases, especially in tumors. These multisubunit enzymes are composed of the Ring finger protein, the Cullin2 scaffold protein, the Elongin B&C linker protein and the variant substrate recognition subunits (SRSs), among which the Cullin2 scaffold protein is the determining factor of the enzyme mechanism. Substrate recognition of Cullin2-type ubiquitin ligases depends on SRSs and results in the degradation of diseases associated substrates by intracellular signaling events. This review focuses on the diversity and the multifunctionality of SRSs in the Cullin2-type ubiquitin ligases, including VHL, LRR-1, FEM1b, PRAME and ZYG11. Recently, as more SRSs are being discovered and more aspects of substrate recognition have been illuminated, insight into the relationship between Cul2-dependent SRSs and substrates provides a new area for cancer research.
Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, China.|The Fourth Clinical College of Nanjing Medical University, Nanjing, China.
Siwei
S
Wang
Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, China.|The Fourth Clinical College of Nanjing Medical University, Nanjing, China.
Wenjia
W
Xia
Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, China.|The Fourth Clinical College of Nanjing Medical University, Nanjing, China.
Mantang
M
Qiu
Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, China.|The Fourth Clinical College of Nanjing Medical University, Nanjing, China.
Xin
X
Wang
Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, China.
Feng
F
Jiang
Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, China.
Rong
R
Yin
Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, China.
Lin
L
Xu
D000951:Antigens, Neoplasm / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology; D018797:Cell Cycle Proteins / Q000502:physiology; D044842:Cullin Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D021122:Protein Subunits; D012097:Repressor Proteins / Q000502:physiology; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000502:physiology
D000951:Antigens, Neoplasm; C105153:CUL2 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D044842:Cullin Proteins; C403492:FEM1B protein, human; C464446:LRR1 protein, human; C404944:PRAME protein, human; D021122:Protein Subunits; D012097:Repressor Proteins; C454941:ZYG11A protein, human; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human
E3 ligase; cullin-ring ligase(CRL); cullin2; substrate recognition subunit (SRS)