Histidine Triad Nucleotide-binding Protein 1 Up-regulates Cellular Levels of p27KIP1 by Targeting ScfSKP2 Ubiquitin Ligase and Src
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چکیده
منابع مشابه
Histidine Triad Nucleotide-binding Protein 1 Up-regulates Cellular Levels of p27 by Targeting Scf Ubiquitin Ligase and Src*
The one or more underlying mechanisms of the tumor suppressing activity of the histidine triad nucleotide-binding protein 1 (HINT1) are not well defined. In this study we found that HINT1 regulates cellular levels of the cyclin-dependent kinase inhibitor p27KIP1 through multiple mechanisms. Increased expression of HINT1 increases cellular levels of p27KIP1, and HINT1 knockdown with small hairpi...
متن کاملKinetic mechanism of human histidine triad nucleotide binding protein 1.
Human histidine triad nucleotide binding protein 1 (hHint1) is a member of a ubiquitous and ancient branch of the histidine triad protein superfamily. hHint1 is a homodimeric protein that catalyzes the hydrolysis of model substrates, phosphoramidate and acyl adenylate, with a high efficiency. Recently, catalytically inactive hHint1 has been identified as the cause of inherited peripheral neurop...
متن کاملPTEN regulates the ubiquitin-dependent degradation of the CDK inhibitor p27KIP1 through the ubiquitin E3 ligase SCFSKP2
The PTEN tumor suppressor acts as a phosphatase for phosphatidylinositol-3,4,5-trisphosphate (PIP3) [1, 2]. We have shown previously that PTEN negatively controls the G1/S cell cycle transition and regulates the levels of p27(KIP1), a CDK inhibitor [3, 4]. Recently, we and others have identified an ubiquitin E3 ligase, the SCF(SKP2) complex, that mediates p27 ubiquitin-dependent proteolysis [5-...
متن کاملStructural characterization of human histidine triad nucleotide-binding protein 2, a member of the histidine triad superfamily.
The histidine triad proteins (HITs) constitute a large and ubiquitous superfamily of nucleotide hydrolases. The human histidine triad nucleotide-binding proteins (hHints) are a distinct class of HITs noted for their acyl-AMP hydrolase and phosphoramidase activity. The first high-resolution crystal structures of hHint2 with and without bound AMP are described. The differences between hHint2 and ...
متن کاملThe ubiquitin ligase itch regulates apoptosis by targeting thioredoxin-interacting protein for ubiquitin-dependent degradation.
Thioredoxin interacting protein (TXNIP) was originally characterized as an endogenous inhibitor of thioredoxin, a key regulator in cellular redox homeostasis. TXNIP is also known to play important roles in tumor growth and metastasis, glucose and lipid metabolism. TXNIP expression is induced by various stress stimuli. However, it has been unclear how TXNIP is down-regulated. Here, we report tha...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2009
ISSN: 0021-9258
DOI: 10.1074/jbc.m804531200