Rb protein down-regulates the stress-activated signals through inhibiting c-Jun n-terminal kinase/stress-activated protein kinase

Jaekyung Shim, Hee Sae Park, Myung Jin Kim, Jihyun Park, Eun Park, Ssang Goo Cho, Soo Jung Eom, Han Woong Lee, Cheol O. Joe, Eui Ju Choi

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The Rb protein is the product of the retinoblastoma susceptibility gene and loss of Rb function is detected in many types of human cancers. Rb plays important roles in the regulation of cell proliferation, differentiation, senescence, and apoptotic cell death. Here we show that Rb can physically interact with c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK), thereby inhibiting intracellular signals mediated by JNK/SAPK. Both in vitro binding and in vitro kinase studies suggest that a carboxyl- terminal domain of Rb containing amino acids 768-928 might be crucial for inhibiting JNK/SAPK. In comparison, Rb did not affect enzymatic activity of either extracellular signal-regulated kinase 1 or p38. Ectopically expressed Rb also abrogated the apoptotic cell death induced by ultraviolet radiation or the activation of MEKK1, an upstream kinase that can stimulate the JNK/SAPK cascade. JNK/SAPK inhibition highlights a novel function of Rb, which may provide a new mechanism by which Rb regulates cell death. JNK/SAPK is a major protein kinase that can be stimulated in response to a variety of cellular stresses. Our results, therefore, suggest that Rb, by inhibiting JNK/SAPK, may act as a negative regulator in stress-activated intracellular signaling cascades.

Original languageEnglish
Pages (from-to)14107-14111
Number of pages5
JournalJournal of Biological Chemistry
Volume275
Issue number19
DOIs
Publication statusPublished - 2000 May 12

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Retinoblastoma Protein
Heat-Shock Proteins
JNK Mitogen-Activated Protein Kinases
Protein Kinases
Phosphotransferases
Down-Regulation
Cell death
Cell Death
Retinoblastoma Genes
Mitogen-Activated Protein Kinase 3
Cell proliferation
Cell Differentiation
Ultraviolet radiation
Cell Proliferation
Radiation
Genes
Chemical activation
Amino Acids

ASJC Scopus subject areas

  • Biochemistry

Cite this

Rb protein down-regulates the stress-activated signals through inhibiting c-Jun n-terminal kinase/stress-activated protein kinase. / Shim, Jaekyung; Park, Hee Sae; Kim, Myung Jin; Park, Jihyun; Park, Eun; Cho, Ssang Goo; Eom, Soo Jung; Lee, Han Woong; Joe, Cheol O.; Choi, Eui Ju.

In: Journal of Biological Chemistry, Vol. 275, No. 19, 12.05.2000, p. 14107-14111.

Research output: Contribution to journalArticle

Shim, Jaekyung ; Park, Hee Sae ; Kim, Myung Jin ; Park, Jihyun ; Park, Eun ; Cho, Ssang Goo ; Eom, Soo Jung ; Lee, Han Woong ; Joe, Cheol O. ; Choi, Eui Ju. / Rb protein down-regulates the stress-activated signals through inhibiting c-Jun n-terminal kinase/stress-activated protein kinase. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 19. pp. 14107-14111.
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