SIVA1 Regulates the Stability of Single-Stranded DNA-Binding Protein 3 Isoforms
Tóm tắt
The assembly of LIM-homeodomain (LIM-HD) transcriptional complex plays important roles in early neuronal development. The stability of LIM-HD is controlled by single-strand binding protein 3 (SSBP3) via a cascade mechanism protecting it from proteasomal degradation. The expression level of SSBP3 has to be precisely regulated. Although a decrease of SSBP3 level is associated with several diseases, the mechanism of SSBP3 downregulation and whether SSBP3 itself is subject to proteasomal degradation remain largely unknown. Two strongly conserved transcripts of the SSBP3 gene, SSBP3a and SSBP3c, were cloned from a human brain cDNA library. By RT-PCR, we show that Ssbp3c is continuously expressed in both embryonic and adult mouse brain, whereas Ssbp3a is restricted to embryonic brain tissue. By co-IP and GST pulldown assays, we identified SIVA1 as a novel SSBP3-binding factor. In a ubiquitination assay, we show that SIVA1 enhances the ubiquitination of SSBP3 and regulates its abundance. Our findings reveal the proteasomal degradation of SSBP3 for the first time and provide a rationale for an SIVA1-SSBP3-dependent mechanism for the disassembly of LIM-HD multiprotein complexes.
Tài liệu tham khảo
Li W., Bengtson M.H., Ulbrich A., Matsuda A., Reddy V.A., Orth A., Chanda S.K., Batalov S., Joazeiro C.A. 2008. Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle’s dynamics and signaling. PLoS One. 3 (1), e1487.
Bayarsaihan D., Soto R.J., Lukens L.N. 1998. Cloning and characterization of a novel sequence-specific single-stranded-DNA-binding protein. Biochem. J. 331 (2), 447‒452.
Chen L., Segal D., Hukriede N.A., Podtelejnikov A.V., Bayarsaihan D., Kennison J.A., Ogryzko V.V., Dawid I.B., Westphal H. 2002. Ssdp proteins interact with the LIM-domain-binding protein Ldb1 to regulate development. Proc. Natl. Acad. Sci. U. S. A. 99, 14 320‒14 325.
van Meyel D.J., Thomas J.B., Agulnick A.D. 2003. Ssdp proteins bind to LIM-interacting co-factors and regulate the activity of LIM-homeodomain protein complexes in vivo. Development. 130, 1915‒1925.
Nishioka N., Nagano S., Nakayama R., Kiyonari H., Ijiri T., Taniguchi K., Shawlot W., Hayashizaki Y., Westphal H., Behringer R.R., Matsuda Y., Sakoda S., Kondoh H., Sasaki H. 2005. Ssdp1 regulates head morphogenesis of mouse embryos by activating the Lim1–Ldb1 complex. Development. 132, 2535‒2546.
Enkhmandakh B., Makeyev A.V., Bayarsaihan D. 2006. The role of the proline-rich domain of Ssdp1 in the modular architecture of the vertebrate head organizer. Proc. Natl. Acad. Sci. U. S. A. 103, 11 631‒11 636.
Gungor C., Taniguchi-Ishigaki N., Ma H., Drung A., Tursun B., Ostendorff H.P., Bossenz M., Becker C.G., Becker T., Bach I. 2007. Proteasomal selection of multiprotein complexes recruited by LIM homeodomain transcription factors. Proc. Natl. Acad. Sci. U. S. A. 104, 15 000‒15 005.
Hiratani I., Yamamoto N., Mochizuki T., Ohmori S.Y., Taira M. 2003. Selective degradation of excess Ldb1 by Rnf12/RLIM confers proper Ldb1 expression levels and Xlim-1/Ldb1 stoichiometry in Xenopus organizer functions. Development. 130, 4161‒4175.
Ostendorff H.P., Peirano R.I., Peters M.A., Schluter A., Bossenz M., Scheffner M., Bach I. 2002. Ubiquitination-dependent cofactor exchange on LIM homeodomain transcription factors. Nature. 416, 99‒103.
Cai Y., Xu Z., Nagarajan L., Brandt S.J. 2008. Single-stranded DNA-binding proteins regulate the abundance and function of the LIM-homeodomain transcription factor LHX2 in pituitary cells. Biochem. Biophys. Res. Commun. 373, 303‒308.
Prasad K.V., Ao Z., Yoon Y., Wu M.X., Rizk M., Jacquot S., Schlossman S.F. 1997. CD27, a member of the tumor necrosis factor receptor family, induces apoptosis and binds to Siva, a proapoptotic protein. Proc. Natl. Acad. Sci. U. S. A. 94, 6346‒6351.
Spinicelli S., Nocentini G., Ronchetti S., Krausz L.T., Bianchini R., Riccardi C. 2002. GITR interacts with the pro-apoptotic protein Siva and induces apoptosis. Cell. Death Differ. 9, 1382‒1384.
Du W., Jiang P., Li N., Mei Y., Wang X., Wen L., Yang X., Wu M. 2009. Suppression of p53 activity by Siva1. Cell. Death Differ. 16, 1493‒1504.
Gudi R., Barkinge J., Hawkins S., Prabhakar B., Kanteti P. 2009. Siva-1 promotes K-48 polyubiquitination of TRAF2 and inhibits TCR-mediated activation of NF-kappaB. J. Environ. Pathol. Toxicol. Oncol. 28, 25‒38.
Fan X., Yang Q., Wang Y., Zhang Y., Wang J., Yuan J., Li Y., Wang Y., Deng Y., Yuan W., Mo X., Wan Y., Ocorr K., Yang X., Wu X. 2011. Cloning and characterization of the cardiac-specific Lrrc10 promoter. BMB Rep. 44, 123‒128.
Johnson J.M., Castle J., Garrett-Engele P., Kan Z., Loerch P.M., Armour C.D., Santos R., Schadt E.E., Stoughton R., Shoemaker D.D. 2003. Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science. 302, 2141‒2144.
Blencowe B.J. 2006. Alternative splicing: New insights from global analyses. Cell. 126, 37‒47.
Albert M.L., Darnell R.B. 2004. Paraneoplastic neurological degenerations: keys to tumour immunity. Nat. Rev. Cancer. 4, 36‒44.
Bachinski L.L., Baggerly K.A., Neubauer V.L., Nixon T.J., Raheem O., Sirito M., Unruh A.K., Zhang J., Nagarajan L., Timchenko L.T., Bassez G., Eymard B., Gamez J., Ashizawa T., Mendell J.R., et al. 2014. Most expression and splicing changes in myotonic dystrophy type 1 and type 2 skeletal muscle are shared with other muscular dystrophies. Neuromuscul. Disord. 24, 227‒240.
Wang X., Zha M., Zhao X., Jiang P., Du W., Tam A.Y., Mei Y., Wu M. 2013. Siva1 inhibits p53 function by acting as an ARF E3 ubiquitin ligase. Nat. Commun. 4, 1551.
Resch U., Schichl Y.M., Winsauer G., Gudi R., Prasad K., de Martin R. 2009. Siva1 is a XIAP-interacting protein that balances NFkappaB and JNK signalling to promote apoptosis. J. Cell. Sci. 122, 2651‒2661.