5GWN

Crystal structure of human RCC2

Summary for 5GWN

• Entry DOI: 10.2210/pdb5gwn/pdb
• Descriptor: Protein RCC2, SULFATE ION (3 entities in total)
• Functional Keywords: seven-bladed propeller, protein binding
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus, nucleolus: Q9P258
• Total number of polymer chains: 1
• Total formula weight: 48436.78

Authors

Liang, L.,Yun, C.H.,Yin, Y.X. (deposition date: 2016-09-12, release date: 2017-09-13, Last modification date: 2023-11-08)

Primary citation

Song, C.,Liang, L.,Jin, Y.,Li, Y.,Liu, Y.,Guo, L.,Wu, C.,Yun, C.H.,Yin, Y.
RCC2 is a novel p53 target in suppressing metastasis.
Oncogene, 37:8-17, 2018

PubMed Abstract: RCC2 (also known as TD60) is a highly conserved protein involved in prognosis in colorectal cancer. However, its relationship with tumor development is less understood. Here we demonstrate a signaling pathway defining regulation of RCC2 and its functions in tumor progression. We report that p53 is a transcriptional regulator of RCC2 that acts through its binding to a palindromic motif in the RCC2 promoter. RCC2 physically interacts and deactivates a small GTPase Rac1 that is known to be involved in metastasis. We solved a high-resolution crystal structure of RCC2 and revealed one RCC1-like domain with a unique β-hairpin that is requisite for RCC2 interaction with Rac1. p53 or RCC2 deficiency leads to activation of Rac1 and deterioration of extracellular matrix sensing (haptotaxis) of surface-bound gradients. Ectopic expression of RCC2 restores directional migration in p53-null cells. Our results demonstrate that p53 and RCC2 signaling is important for regulation of cell migration and suppression of metastasis. We propose that the p53/RCC2/Rac1 axis is a potential target for cancer therapy.

PubMed: 28869598
DOI: 10.1038/onc.2017.306

Experimental method

X-RAY DIFFRACTION (1.309 Å)