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NOB1

Official Full Name
NIN1 (RPN12) binding protein 1 homolog
Organism
Homo sapiens
GeneID
28987
Background
In yeast, over 200 protein and RNA cofactors are required for ribosome assembly, and these are generally conserved in eukaryotes. These factors orchestrate modification and cleavage of the initial 35S precursor rRNA transcript into the mature 18S, 5.8S, and 25S rRNAs, folding of the rRNA, and binding of ribosomal proteins and 5S RNA. Nob1 is involved in pre-rRNA processing. In a late cytoplasmic processing step, Nob1 cleaves a 20S rRNA intermediate at cleavage site D to produce the mature 18S rRNA (Lamanna and Karbstein, 2009 [PubMed 19706509]).[supplied by OMIM, Nov 2010]
Synonyms
ART-4; NOB1P; MST158; MSTP158; PSMD8BP1;

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Detailed Information

NOB1 gene is a newly discovered gene in recent years. The encoded protein is a multifunctional nucleoprotein that participates in the assembly of the 40S small subunit of the ribosome, the synthesis and assembly of the 26S proteasome, and the regulation of the cell cycle. Studies have reported that NOB1 is related to tumorigenesis and development, and is expected to become a new target for tumor gene targeted therapy. The N-terminus of the protein contains a PIN domain (Pill Taminoterminus), and the C-terminus contains a ZNRD1 domain (Zincribbon).

NOB1 Figure 1. Abridged general view for the interplay among miR-646, NOB1 and the MAPK pathway in ccRCC. (Li, W. , et al. 2014)

Biological Functions of NOB1

NOB1 may participate in the regulation of the cell cycle through the QNRD1 domain. The QNRD1 domain is homologous to the zinc band domain of TFIS. It was the first nucleic acid binding domain found in yeast transcription factor IIS (TFIIS). This domain contains a triple-stranded antiparallel β-sheet layer and disordered heterocycles, and is highly conserved in evolution. It is a motif that is ubiquitous in eukaryotic and prokaryotic transcription. It is a functional domain that is involved in the transcription of biological response cells. The C-terminus of NOB1 contains a QNRD1 domain. Based on the relationship between QNRD1 and cell cycle regulators and a variety of homologous zinc band motifs were found to be involved in transcription. NOB1 may play an important regulatory role in cell growth and proliferation through its C-terminal ZNRD1 domain, which is related to transcriptional regulation.

The ubiquitin-proteasome pathway (UPP) is an important protein degradation mechanism in cells. NOB1 binds to the 19SRP component of the proteasome and acts as a molecular chaperone, promoting the maturation of the 26S proteasome. Therefore, NOB1 protein is indispensable in the mechanism of UPP-dependent proteolysis. The mutation and abnormal expression of NOB1 will cause the accumulation of polyubiquitin protein in the cell, which will cause the abnormality of the ubiquitin-proteasome system, reduce its degradation of oncoproteins, tumor suppressor proteins, and inhibit the apoptosis of mutant cells,leading to the occurrence of tumors.

NOB1 and Tumor

The expression of NOB1 is low in normal ovarian tissue. Studies have found that the expression level of NOB1 in SKVO3 ovarian cancer cells is higher than that in adjacent tissues and normal tissues, suggesting that the upregulation of NOB1 expression may be closely related to the development of ovarian cancer. The study further applied RNA interference technology to silence NOB1 and found that it can significantly inhibit the proliferation of ovarian cancer cells, and the cell cycle is blocked in the G1 phase. Further research found that the expression level of NOB1 was negatively correlated with the expression level of miR-363 in nested cancer tissues, and miR-363 exerted a tumor suppressor effect by inhibiting the expression of NOB1 in ovarian cancer. It is thought that interference with the transcription and expression of the NOB1 gene in ovarian cancer may effectively inhibit the proliferation of ovarian tumor cells. In addition, studies have found that down-regulating the expression of NOB1 in SKVO3 ovarian cancer cells can significantly increase the therapeutic sensitivity of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Therefore, NOB1 is expected to become a therapeutic target for ovarian cancer.

References:

  1. Li, W. , Liu, M. , Feng, Y. , Xu, Y. F. , Huang, Y. F. , & Che, J. P. , et al. (2014). Downregulated mir-646 in clear cell renal carcinoma correlated with tumour metastasis by targeting the nin one binding protein (nob1). British Journal of Cancer, 111(6), 1188-1200.
  2. Li, Y., Ma, C., Qian, M., Wen, Z., Jing, H., & Qian, D. (2014). Downregulation of nob1 suppresses the proliferation and tumor growth of non-small cell lung cancer in vitro and in vivo. Oncology Reports, 31(3), 1271---1276.
  3. Kun Liu, Ming-Ming Gu, Hong-Lin Chen, & Qing-Sheng You. (2014). Nob1 in non-small-cell lung cancer: expression profile and clinical significance. Pathology & Oncology Research, 20(2), 461-466.
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