Alternative titles; symbols
HGNC Approved Gene Symbol: NOP53
Cytogenetic location: 19q13.33 Genomic coordinates (GRCh38) : 19:47,745,546-47,757,058 (from NCBI)
Smith et al. (2000) generated a complete transcript map of a 150-kb interval of chromosome 19q13.3 in which allelic loss is a frequent event in human diffuse gliomas. Using cDNA selection with whole brain and placenta poly(A)+ RNAs, exon trapping, and genomic sequencing, they identified 2 novel transcripts, designated GLTSCR1 (605690) and GLTSCR2. The full-length coding region of GLTSCR2 was identified by direct cDNA selection, exon trapping, and the assembly of multiple ESTs. Northern blot analysis detected expression of a 1.5-kb GLTSCR2 transcript at high levels in heart and pancreas, moderate levels in placenta, liver, skeletal muscle, and kidney, and low levels in brain and lung.
Using a C-terminal domain of PTEN (601728) as bait in a yeast 2-hybrid screen of a brain cDNA library, Okahara et al. (2004) cloned GLTSCR2, which they designated PICT1.
By in vitro protein binding assays with recombinant proteins, and by coimmunoprecipitation of endogenous proteins, Okahara et al. (2004) confirmed the interaction between PTEN and GLTSCR2. The interaction required amino acids 338 through 348 of GLTSCR2 and a C-terminal segment of PTEN that did not include the PDZ domain. Downregulation of GLTSCR2 in breast carcinoma cells by RNA interference enhanced the degradation of PTEN with concomitant decrease in PTEN phosphorylation. PTEN C-terminal tumor-associated mutants, which are highly susceptible to protein degradation, were unable to bind GLTSCR2 and showed reduced phosphorylation. Okahara et al. (2004) concluded that GTSCR2 interacts directly with PTEN and promotes its phosphorylation and stability.
Sasaki et al. (2011) found that conditional deletion of Pict1 expression in mouse embryonic stem (ES) cells inhibited cell growth due to cell cycle arrest and enhanced apoptosis. Mass spectrometric analysis of peptides that immunoprecipitated with epitope-tagged PICT1 in transfected 293T cells showed that PICT1 interacted with RPL11 (604175), a ribosomal protein that binds to MDM2 (164785) and inhibits MDM2-mediated ubiquitination of the tumor suppressor p53 (TP53; 191170). Knockdown of Pict1 in mouse ES cells resulted in translocation of Rpl11 from the nucleolus to the nucleoplasm, permitting its interaction with Mdm2. Examination of PICT1 levels in human colorectal and esophageal cancers showed that low PICT1 expression was associated with low tumor growth and better patient survival. Sasaki et al. (2011) concluded that PICT1 is a potent regulator of the MDM2-p53 pathway.
By sequence analysis, Smith et al. (2000) mapped the GLTSCR2 gene to chromosome 19q13.3
Sasaki et al. (2011) found that Pict1 deletion in mice was embryonic lethal. Pict1-null embryos appeared normal until the morula stage at embryonic day 2.75 (E2.75), but no embryos formed proper blastocysts at E3.5, and all contained apoptotic cells.
Okahara, F., Ikawa, H., Kanaho, Y., Maehama, T. Regulation of PTEN phosphorylation and stability by a tumor suppressor candidate protein. J. Biol. Chem. 279: 45300-45303, 2004. [PubMed: 15355975] [Full Text: https://doi.org/10.1074/jbc.C400377200]
Sasaki, M., Kawahara, K., Nishio, M., Mimori, K., Kogo, R., Hamada, K., Itoh, B., Wang, J., Komatsu, Y., Yang, Y. R., Hikasa, H., Horie, Y., and 11 others. Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11. Nature Med. 17: 944-951, 2011. [PubMed: 21804542] [Full Text: https://doi.org/10.1038/nm.2392]
Smith, J. S., Tachibana, I., Pohl, U., Lee, H. K., Thanarajasingam, U., Portier, B. P., Ueki, K., Ramaswamy, S., Billings, S. J., Mohrenweiser, H. W., Louis, D. N., Jenkins, R. B. A transcript map of the chromosome 19q-arm glioma tumor suppressor region. Genomics 64: 44-50, 2000. [PubMed: 10708517] [Full Text: https://doi.org/10.1006/geno.1999.6101]