JOURNAL OF SHANDONG UNIVERSITY(NATURAL SCIENCE) ›› 2015, Vol. 50 ›› Issue (01): 37-41.doi: 10.6040/j.issn.1671-9352.0.2014.412

Previous Articles     Next Articles

Degradation of co-activator Yki of the hippo pathway through ubiquitinationby Slimb

GUO JI-wei, JIN Dan   

  1. School of Life Sciences, Nankai University, Tianjin 300071, China
  • Received:2014-09-17 Revised:2014-11-07 Online:2015-01-20 Published:2015-01-24

Abstract: Yki, an important co-transcription factor, regulates the expression of downstream target genes of the hippo pathway. Yki is known to be important for development, growth, organogenesis and maintenance of adult stem cells. Slimb as a substrate specificity subunit of the SCF E3 ubiquitin ligase promotes proteins for degradation in the drosophila. In this paper, we found that Slimb degraded Yki by the ubiquitination and the co-immunoprecipitation indicated that Slimb interacted with Yki in vitro. Furthermore, we found that co-overexpression with Slimb caused mostly suppressed Yki wing phenotype and knockdown of Slimb enhanced overexpression with Yki eye phenotype. These results suggested that Slimb as a subunit of the E3 ubiquitin ligase regulated the stability of Yki and provided an important significance in the regulating tissue growth and development of hippo pathway.

Key words: hippo pathway, yki, ubiquitination, degradation, slimb

CLC Number: 

  • Q257
[1] WU S A, HUANG J B, DONG J, et al. Hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts[J]. Cell, 2003, 114(4):445-456.
[2] PAN Doujia. The hippo signaling pathway in development and cancer [J]. Dev Cell, 2010, 19(4):491-505.
[3] YU F X, ZHANG Y, PARK H W, et al. Protein kinase a activates the Hippo pathway to modulate cell proliferation and differentiation [J]. Genes Dev, 2013, 27(11):1223-1232.
[4] YU F X, GUAN K L.The hippo pathway: regulators and regulations [J]. Genes Dev, 2013, 27(4):355-371.
[5] DUPONT S, MORSUT L, ARAGONA M, et al. Role of YAP/TAZ in mechanotransduction[J]. Nature, 2011, 474(7350):179-183.
[6] HONG W, GUAN K L.The YAP and TAZ transcription co-activators: key downstream effectors of the mammalian hippo pathway [J]. Semin Cell Dev Biol, 2012, 23(7):785-793.
[7] CHEN C L, SCHROEDER M C, KANGO-SINGH M, et al. Tumor suppression by cell competition through regulation of the hippo pathway[J]. PNAS, 2012, 109(2):484-489.
[8] ZHAO B, LI L, LU Q, et al. Angiomotin is a novel Hippo pathway component that inhibitsYAP oncoprotein [J]. Genes Dev, 2011, 25(1):51-63.
[9] CAI J, ZHANG N, ZHENG Y, et al. The hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program [J]. Genes Dev, 2010, 24(21):2383-2388.
[10] KARPOWICZ P, PEREZ J, PERRIMON N. The Hippo tumor suppressor pathway regulatesintestinal stem cell regeneration[J]. Development, 2010, 137(24):4135-4145.
[11] REN F, WANG B, YUE T, et al. Hippo signaling regulates drosophila intestine stem cell proliferation through multiple pathways[J]. PNAS, 2010, 107(49):21064-21069.
[12] CORDENONSI M, ZANCONATO F, AZZOLIN L. The hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells[J]. Cell, 2011, 147(4):759-772.
[13] SUN G, IRVINE K D. Regulation of hippo signaling by Jun kinase signaling during compensatory cell proliferation and regeneration, and in neoplastic tumors [J]. Dev Biol, 2011, 350(1):139-151.
[14] GURDA G T, ZHU Q, BAI H, et al. The use of Yes-associated protein expression in the diagnosis of persistent neonatal cholestatic liver disease [J]. Hum Pathol, 2014, 45(5):1057-1064.
[15] CHEN Q, ZHANG N, GRAY R S, et al. A temporal requirement for hippo signaling in mammary gland differentiation, growth, and tumorigenesis [J]. Genes Dev, 2014, 28(5):432-437.
[16] STEINHARDT A A, GAYYED M F, KLEIN A P, et al. Expression of yes-associated protein in common solid tumors [J]. Hum Pathol, 2008, 39(11):1582-1589.
[17] JIANG J, STRUHL G. Regulation of the hedgehog and wingless signaling pathways by the F-box/WD40-repeat protein slimb[J]. Nature, 1998, 391(6666):493-496.
[18] GRIMA B, LAMOUROUX A, CHELOT E. The F-box protein slimb controls the levels of clock proteins period and timeless[J]. Nature, 2002, 420(6912):178-182.
[19] ADOLPHE C, NARANG M, ELLIS T, et al. An in vivo comparative study of sonic, desert and Indian hedgehog reveals that hedgehog pathway activity regulates epidermal stem cell homeostasis[J]. Development, 2004, 131(20):5009-5019.
[20] FUCHS S Y, SPIEGELMAN V S, SURESH KUMAR K G. The many faces of beta-TrCP E3 ubiquitin ligases: reflections in the magic mirror of cancer[J]. Oncogene, 2004, 23(11):2028-2036.
[21] SKAAR J R, PAGAN J K, PAGANO M.Mechanisms and function of substrate recruitmentby F-box proteins[J]. Nat Rev Mol Cell Biol, 2013, 14(6):369-381.
[22] KO H W, JIANG J, EDERY I.Role for Slimb in the degradation of drosophila periodprotein phosphorylated by doubletime[J]. Nature, 2002, 420(6916):673-681.
[23] EURICO Morais-de-S, AVIK Mukherjee, NICK Lowe, et al. Slmb antagonises the aPKC/Par-6 complex to control oocyte and epithelial polarity[J]. Development, 2014, 141(10):2984-2992.
[24] LARA C Skwarek, SARAH L Windler, GEERT de Vreede, et al. The F-box protein Slmb restricts the activity of aPKC to polarize epithelial cells[J]. Development, 2014, 141(10):2978-2983.
[25] ZHAO B, LI L, TUMANENG K, et, al. A coordinated phosphorylation by lats and CK1 regulates YAP stability through SCF(beta-TRCP)[J]. Genes Dev, 2010, 24(1):72-85.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!