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Gene Review

SCRIB  -  scribbled planar cell polarity protein

Homo sapiens

Synonyms: CRIB1, KIAA0147, LAP4, Protein LAP4, Protein scribble homolog, ...
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Disease relevance of SCRIB

  • The hScrib/Dlg apico-basal control complex is differentially targeted by HPV-16 and HPV-18 E6 proteins [1].
  • In this study, we have examined the abilities of E6 proteins from HPV-16 and HPV-18 to interact with and induce the degradation of two PDZ domain-containing targets, Dlg and hScrib [1].
  • We demonstrate that Tax can bind to hScrib and that the resulting Tax/hScrib complex is present in human T cell leukemia virus type 1-infected T cells [2].

High impact information on SCRIB

  • An additional component of polarity is a family of polarity proteins in T cells that includes Dlg, Scrib and Lgl, as well as a complex of partitioning-defective proteins [3].
  • We used dominant-negative constructs and small interfering RNA to show that TSHR recycling is regulated by the interaction between hScrib and betaPIX, and by the activity of GIT1 [4].
  • We previously demonstrated that hScrib is associated with a betaPIX-GIT1 complex comprised of a guanine nucleotide exchange factor and a GTPase-activating protein for ADP ribosylation factors that is involved in vesicle trafficking [4].
  • We now show that knockdown of Scrib disrupts adhesion between Madin-Darby canine kidney epithelial cells [5].
  • Thus, the high-risk HPV E6 proteins induce the degradation of the human homologs of two Drosophila PDZ domain-containing tumor suppressor proteins, hDlg and hScrib, both of which are associated with cell junction complexes [6].

Biological context of SCRIB


Anatomical context of SCRIB

  • Whereas LPP is also localized in focal adhesions and in the nucleus, Scrib could not be detected at these locations in MDCKII and CV-1 cells [7].
  • In neoplasia, alterations in the expression pattern of hDlg and of hScrib increase during tumor progression; down-regulation of both proteins being associated with lack of epithelial cell polarity and disorganized tissue architecture [9].
  • Green fluorescent protein-hScrib was localized to the periphery of MDCK cells, where it colocalized with ZO-1, a component of tight junctions [6].
  • RESULTS: Depletion of Scrib by siRNA or expression of dominant-negative constructs inhibits astrocyte polarization [10].
  • Like Cdc42, Scrib controls protrusion formation, cytoskeleton polarization, and centrosome and Golgi reorientation [10].

Associations of SCRIB with chemical compounds

  • When given as posttreatment, the group II agonists LCCG1 (100 microM, n = 5) and LY379268 (100 microM, n = 6) and the group III agonist LAP4 (100 microM, n = 6) reversed the capsaicin-induced sensitization [12].
  • Cross-linking yields do not change irrespective of whether active Crib* replaces an outer or an inner (target) deoxycytidine within the EcoRII recognition site [13].

Physical interactions of SCRIB

  • We show that TRIP6 directly binds to the third PDZ domain of Scrib via its carboxy-terminus [14].
  • Previously, we established that LPP interacts with the tumor suppressor Scrib, a member of the leucine-rich repeat and PDZ (LAP) family of proteins [14].
  • The tumor suppressor Scrib selectively interacts with specific members of the zyxin family of proteins [14].

Regulatory relationships of SCRIB


Other interactions of SCRIB

  • The PDZ proteins such as hDLG, hScrib and MAGIs function as the membrane-associated protein scaffolds and have been shown to interact with the high-risk human papillomavirus (HPV) E6s [16].
  • Our data provide additional insights on the modalities of recruitment of hScrib at the cell-cell junctions, and establish a potential link between the E-cadherin and hScrib tumor suppressors [8].
  • Scrib has been shown to interact with betaPIX, a guanine nucleotide exchange factor for the small GTPases Rac and Cdc42 [10].
  • To investigate how basolateral LAP proteins (LRR (for leucine-rich repeats) and PDZ (for PSD-95/Discs-large/ZO-1), which play key roles in cell polarity, reach their target membrane, we carried out a structure-function study of three LAP proteins: Caenorhabditis elegans LET-413, human Erbin and human Scribble (hScrib) [17].
  • Scribble has a human homologue, human scribble (hScrib), which is a substrate of ubiquitin-mediated degradation by human papillomavirus E6 and the E6AP ubiquitin-protein ligase [18].

Analytical, diagnostic and therapeutic context of SCRIB


  1. The hScrib/Dlg apico-basal control complex is differentially targeted by HPV-16 and HPV-18 E6 proteins. Thomas, M., Massimi, P., Navarro, C., Borg, J.P., Banks, L. Oncogene (2005) [Pubmed]
  2. The PDZ domain-binding motif of the human T cell leukemia virus type 1 tax protein induces mislocalization of the tumor suppressor hScrib in T cells. Arpin-André, C., Mesnard, J.M. J. Biol. Chem. (2007) [Pubmed]
  3. Maintenance and modulation of T cell polarity. Krummel, M.F., Macara, I. Nat. Immunol. (2006) [Pubmed]
  4. Thyrotropin receptor trafficking relies on the hScrib-betaPIX-GIT1-ARF6 pathway. Lahuna, O., Quellari, M., Achard, C., Nola, S., Méduri, G., Navarro, C., Vitale, N., Borg, J.P., Misrahi, M. EMBO J. (2005) [Pubmed]
  5. The mammalian Scribble polarity protein regulates epithelial cell adhesion and migration through E-cadherin. Qin, Y., Capaldo, C., Gumbiner, B.M., Macara, I.G. J. Cell Biol. (2005) [Pubmed]
  6. Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase. Nakagawa, S., Huibregtse, J.M. Mol. Cell. Biol. (2000) [Pubmed]
  7. The tumor suppressor Scrib interacts with the zyxin-related protein LPP, which shuttles between cell adhesion sites and the nucleus. Petit, M.M., Meulemans, S.M., Alen, P., Ayoubi, T.A., Jansen, E., Van de Ven, W.J. BMC Cell Biol. (2005) [Pubmed]
  8. Junctional recruitment of mammalian Scribble relies on E-cadherin engagement. Navarro, C., Nola, S., Audebert, S., Santoni, M.J., Arsanto, J.P., Ginestier, C., Marchetto, S., Jacquemier, J., Isnardon, D., Le Bivic, A., Birnbaum, D., Borg, J.P. Oncogene (2005) [Pubmed]
  9. Human discs large and scrib are localized at the same regions in colon mucosa and changes in their expression patterns are correlated with loss of tissue architecture during malignant progression. Gardiol, D., Zacchi, A., Petrera, F., Stanta, G., Banks, L. Int. J. Cancer (2006) [Pubmed]
  10. Scrib Controls Cdc42 Localization and Activity to Promote Cell Polarization during Astrocyte Migration. Osmani, N., Vitale, N., Borg, J.P., Etienne-Manneville, S. Curr. Biol. (2006) [Pubmed]
  11. hScrib interacts with ZO-2 at the cell-cell junctions of epithelial cells. Métais, J.Y., Navarro, C., Santoni, M.J., Audebert, S., Borg, J.P. FEBS Lett. (2005) [Pubmed]
  12. Groups II and III metabotropic glutamate receptors differentially modulate brief and prolonged nociception in primate STT cells. Neugebauer, V., Chen, P.S., Willis, W.D. J. Neurophysiol. (2000) [Pubmed]
  13. Affinity modification of EcoRII DNA methyltransferase by the dialdehyde-substituted DNA duplexes: mapping the enzyme region that interacts with DNA. Gritsenko, O.M., Koudan, E.V., Mikhailov, S.N., Ermolinsky, B.S., Van Aerschot, A., Herdewijn, P., Gromova, E.S. Nucleosides Nucleotides Nucleic Acids (2002) [Pubmed]
  14. The tumor suppressor Scrib selectively interacts with specific members of the zyxin family of proteins. Petit, M.M., Crombez, K.R., Vervenne, H.B., Weyns, N., Van de Ven, W.J. FEBS Lett. (2005) [Pubmed]
  15. Human homolog of Drosophila tumor suppressor Scribble negatively regulates cell-cycle progression from G1 to S phase by localizing at the basolateral membrane in epithelial cells. Nagasaka, K., Nakagawa, S., Yano, T., Takizawa, S., Matsumoto, Y., Tsuruga, T., Nakagawa, K., Minaguchi, T., Oda, K., Hiraike-Wada, O., Ooishi, H., Yasugi, T., Taketani, Y. Cancer Sci. (2006) [Pubmed]
  16. Human papillomavirus type 16 E6 protein interacts with cystic fibrosis transmembrane regulator-associated ligand and promotes E6-associated protein-mediated ubiquitination and proteasomal degradation. Jeong, K.W., Kim, H.Z., Kim, S., Kim, Y.S., Choe, J. Oncogene (2007) [Pubmed]
  17. Basolateral targeting by leucine-rich repeat domains in epithelial cells. Legouis, R., Jaulin-Bastard, F., Schott, S., Navarro, C., Borg, J.P., Labouesse, M. EMBO Rep. (2003) [Pubmed]
  18. Analysis of the expression and localisation of a LAP protein, human scribble, in the normal and neoplastic epithelium of uterine cervix. Nakagawa, S., Yano, T., Nakagawa, K., Takizawa, S., Suzuki, Y., Yasugi, T., Huibregtse, J.M., Taketani, Y. Br. J. Cancer (2004) [Pubmed]
  19. Mammalian Scribble forms a tight complex with the betaPIX exchange factor. Audebert, S., Navarro, C., Nourry, C., Chasserot-Golaz, S., Lécine, P., Bellaiche, Y., Dupont, J.L., Premont, R.T., Sempéré, C., Strub, J.M., Van Dorsselaer, A., Vitale, N., Borg, J.P. Curr. Biol. (2004) [Pubmed]
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