5JZV

The structure of D77G hCINAP-ADP

Summary for 5JZV

• Entry DOI: 10.2210/pdb5jzv/pdb
• Descriptor: Adenylate kinase isoenzyme 6, ADENOSINE-5'-DIPHOSPHATE (3 entities in total)
• Functional Keywords: atpase, adenylate kinase, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus, nucleoplasm: Q9Y3D8
• Total number of polymer chains: 1
• Total formula weight: 24004.52

Authors

Liu, Y.,Yang, Z.,Yang, Y.,Cai, X.,Zheng, X. (deposition date: 2016-05-17, release date: 2016-08-10, Last modification date: 2023-11-08)

Primary citation

Bai, D.,Zhang, J.,Li, T.,Hang, R.,Liu, Y.,Tian, Y.,Huang, D.,Qu, L.,Cao, X.,Ji, J.,Zheng, X.
The ATPase hCINAP regulates 18S rRNA processing and is essential for embryogenesis and tumour growth.
Nat Commun, 7:12310-12310, 2016

PubMed Abstract: Dysfunctions in ribosome biogenesis cause developmental defects and increased cancer susceptibility; however, the connection between ribosome assembly and tumorigenesis remains unestablished. Here we show that hCINAP (also named AK6) is required for human 18S rRNA processing and 40S subunit assembly. Homozygous CINAP(-/-) mice show embryonic lethality. The heterozygotes are viable and show defects in 18S rRNA processing, whereas no delayed cell growth is observed. However, during rapid growth, CINAP haploinsufficiency impairs protein synthesis. Consistently, hCINAP depletion in fast-growing cancer cells inhibits ribosome assembly and abolishes tumorigenesis. These data demonstrate that hCINAP reduction is a specific rate-limiting controller during rapid growth. Notably, hCINAP is highly expressed in cancers and correlated with a worse prognosis. Genome-wide polysome profiling shows that hCINAP selectively modulates cancer-associated translatome to promote malignancy. Our results connect the role of hCINAP in ribosome assembly with tumorigenesis. Modulation of hCINAP expression may be a promising target for cancer therapy.

PubMed: 27477389
DOI: 10.1038/ncomms12310

Experimental method

X-RAY DIFFRACTION (2.07 Å)