Regulation of proto-oncogenic dbl by chaperone-controlled, ubiquitin-mediated degradation.

Regulation of proto-oncogenic dbl by chaperone-controlled, ubiquitin-mediated degradation. Research Abstract Details 

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Regulation of proto-oncogenic dbl by chaperone-controlled, ubiquitin-mediated degradation. Abstract Text:

Elena Kamynina,Krista Kauppinen,Faping Duan,Nora Muakkassa,Danny Manor,

The dbl proto-oncogene product is a prototype of a growing family of guanine nucleotide exchange factors (GEFs) that stimulate the activation of small GTP-binding proteins from the Rho family. Mutations that result in the loss of proto-Dbl's amino terminus produce a variant with constitutive GEF activity and high oncogenic potential. Here, we show that proto-Dbl is a short-lived protein that is kept at low levels in cells by efficient ubiquitination and degradation. The cellular fate of proto-Dbl is regulated by interactions with the chaperones Hsc70 and Hsp90 and the protein-ubiquitin ligase CHIP, and these interactions are mediated by the spectrin domain of proto-Dbl. We show that CHIP is the E3 ligase responsible for ubiquitination and proteasomal degradation of proto-Dbl, while Hsp90 functions to stabilize the protein. Onco-Dbl, lacking the spectrin homology domain, cannot bind these regulators and therefore accumulates in cells at high levels, leading to persistent stimulation of its downstream signaling pathways.

Regulation of proto-oncogenic dbl by chaperone-controlled, ubiquitin-mediated degradation. Publishing Authors By Initials

E Kamynina,K Kauppinen,F Duan,N Muakkassa,D Manor,

For similar enzymes and coenzymes: enzymes: ligases: ubiquitin-protein ligase complexes: ubiquitin-protein ligases research abstracts see: enzymes and coenzymes: enzymes: ligases: ubiquitin-protein ligase complexes: ubiquitin-protein ligases research

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Regulation of proto-oncogenic dbl by chaperone-controlled, ubiquitin-mediated degradation. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular and cellular biology

VOLUME: 27

Page Numbers: 1809-22

Journal Abbreviation: Mol. Cell. Biol.

ISSN: 0270-7306

DAY: 18

MONTH: 12

YEAR: 2006

Regulation of proto-oncogenic dbl by chaperone-controlled, ubiquitin-mediated degradation. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8109087

Regulation of proto-oncogenic dbl by chaperone-controlled, ubiquitin-mediated degradation. Keywords Mesh Terms:

KEYWORDS: Ubiquitin-Protein Ligases

MESH TERMS: metabolism

Chemical & Substance for Abstract: Regulation of proto-oncogenic dbl by chaperone-controlled, ubiquitin-mediated degradation. Information

Substance Name: Ubiquitin-Protein Ligases

Registry Number: EC 6.3.2.19

Grant and Affiliation Information for Regulation of proto-oncogenic dbl by chaperone-controlled, ubiquitin-mediated degradation.

AFFILIATION: Case School of Medicine, WG-48, Case Western Reserve University, Cleveland, OH 44106, USA. danny.manor@case.edu

Country: United States

AGENCY: United States NIDDK

GRANT: T32DK-007158-30

ACRONYM: DK

MEDLINETA: Mol Cell Biol

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