KIBRA regulates hippo signaling activity via interactions with large tumor suppressor kinases

Ling Xiao, Yuanhong Chen, Ming Ji, Jixin Dong

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

The Hippo pathway controls tissue growth and tumorigenesis by inhibiting cell proliferation and promoting apoptosis. Recent genetic studies in Drosophila identified Kibra as a novel regulator of Hippo signaling. Human KIBRA has been associated with memory performance and cell migration. However, it is unclear whether or how KIBRA is connected to the Hippo pathway in mammalian cells. Here, we show that KIBRA associates with and activates Lats (large tumor suppressor) 1 and 2 kinases by stimulating their phosphorylation on the hydrophobic motif. KIBRA overexpression stimulates the phosphorylation of Yes-associated protein (YAP), the Hippo pathway effector. Conversely, depletion of KIBRA by RNA interference reduces YAP phosphorylation. Furthermore, KIBRA stabilizes Lats2 by inhibiting its ubiquitination. We also found that KIBRA mRNA is induced by YAP overexpression in both murine and human cells, suggesting the evolutionary conservation of KIBRA as a transcriptional target of the Hippo signaling pathway. Thus, our study revealed a new connection between KIBRA and mammalian Hippo signaling.

Original languageEnglish (US)
Pages (from-to)7788-7796
Number of pages9
JournalJournal of Biological Chemistry
Volume286
Issue number10
DOIs
StatePublished - Mar 11 2011

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Phosphorylation
Tumors
Phosphotransferases
Cells
Neoplasms
Proteins
Ubiquitination
Cell proliferation
RNA Interference
Drosophila
Cell Movement
Conservation
Carcinogenesis
Cell Proliferation
RNA
Tissue
Apoptosis
Data storage equipment
Messenger RNA
Growth

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

KIBRA regulates hippo signaling activity via interactions with large tumor suppressor kinases. / Xiao, Ling; Chen, Yuanhong; Ji, Ming; Dong, Jixin.

In: Journal of Biological Chemistry, Vol. 286, No. 10, 11.03.2011, p. 7788-7796.

Research output: Contribution to journalArticle

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