Uncovering residues that regulate cyclin D1 proteasomal degradation.

Uncovering residues that regulate cyclin D1 proteasomal degradation. Research Abstract Details 

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Uncovering residues that regulate cyclin D1 proteasomal degradation. Abstract Text:

Q Feng,D Sekula,R ,S J Freemantle,E Dmitrovsky,

Cyclin D1 regulates G1 cell-cycle progression and is aberrantly expressed in carcinogenesis. Proteasomal degradation of cyclin D1 was highlighted as a cancer chemopreventive mechanism. To understand this mechanism better, residues responsible for degradation and ubiquitination of cyclin D1 were investigated. Eighteen lysines in cyclin D1 had single, double or multiple mutations engineered before transfection into BEAS-2B human bronchial epithelial (HBE) cells to evaluate stabilities after all-trans-retinoic acid (RA) or cycloheximide treatments. Specific mutations stabilized cyclin D1, including substitutions of lysines surrounding the cyclin box domain that inhibited RA-mediated degradation and extended the cyclin D1 half-life. Mutation of all cyclin D1 lysines blocked polyubiquitination. N-terminus (but not C-terminus) modification stabilized cyclin D1. Ubiquitination-resistant mutants preferentially localized cyclin D1 to the nucleus, directly implicating subcellular localization in regulating cyclin D1 degradation. Taken together, these findings uncover specific residues conferring ubiquitination of cyclin D1. These provide a mechanistic basis for proteasomal degradation of cyclin D1.

Uncovering residues that regulate cyclin D1 proteasomal degradation. Publishing Authors By Initials

Q Feng,D Sekula,R ,SJ Freemantle,E Dmitrovsky,

For similar proteins: ubiquitins: ubiquitin research abstracts see: proteins: ubiquitins: ubiquitin research

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Uncovering residues that regulate cyclin D1 proteasomal degradation. Journal Published:

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

Journal: Oncogene

VOLUME: 26

Page Numbers: 5098-106

Journal Abbreviation: Oncogene

ISSN: 0950-9232

DAY: 19

MONTH: 02

YEAR: 2007

Uncovering residues that regulate cyclin D1 proteasomal degradation. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8711562

Uncovering residues that regulate cyclin D1 proteasomal degradation. Keywords Mesh Terms:

KEYWORDS: Ubiquitin

MESH TERMS: metabolism

Chemical & Substance for Abstract: Uncovering residues that regulate cyclin D1 proteasomal degradation. Information

Substance Name: Proteasome Endopeptidase Complex

Registry Number: EC 3.4.25.1

Grant and Affiliation Information for Uncovering residues that regulate cyclin D1 proteasomal degradation.

AFFILIATION: Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03755, USA.

Country: England

AGENCY: United States NCI

GRANT: R01 CA111422

ACRONYM: CA

MEDLINETA: Oncogene

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Number Hits: 0

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