Degradation of tyrosine aminotransferase (TAT) via the ubiquitin–proteasome pathway

Gross-Mesilaty, Shlomit; Hargrove, James L.; Ciechanover, Aaron

doi:10.1016/s0014-5793(97)00181-6

Cited by 27 publications

(14 citation statements)

References 20 publications

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“…19) PLP can bind lysine residues by schiff base to affect protein properties. Since ubiquitination also occurs on lysine residues, PLP may hide lysine residues representing polyubiquitination sites on proteins, thereby preventing ubiquitin-mediated protein degradation and prolonging protein activity in the cell.…”

Section: Discussionmentioning

confidence: 99%

Growth suppression and cell death by pyridoxal is dependent on p53 in the human breast cancer cell line MCF-7

Minamino

Oka

Kanouchi

2015

Bioscience, Biotechnology, and Biochemistry

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Vitamin B6 compound, pyridoxine (PN), has shown antitumor action. Our previous experiments showed that PN induces expression of insulin-like growth factor binding protein-3 to arrest proliferation and induce cell death. This induction is inhibited by the p53-specific inhibitor pifithrin-α. Here, we report that another B6 compound, pyridoxal (PL), strongly inhibited MCF-7 cell growth compared to PN. PL induced the G0/G1 arrest and the accumulation of subG1 population. Although p53 mRNA was not changed by PL, 0.5 mM PL increased the protein level in MCF-7 cells. The cell growth suppression by 0.5 mM PL did not occur when p53 expression was knocked down using siRNA. Together, these data suggest that PL accumulate p53 and PL-induced cell growth suppression is dependent on p53 in MCF-7 breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

Growth suppression and cell death by pyridoxal is dependent on p53 in the human breast cancer cell line MCF-7

Minamino

Oka

Kanouchi

2015

Bioscience, Biotechnology, and Biochemistry

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“…In hTAT, the first 38 amino acids may not be involved in enzyme dimerization, and are not required in the active site stability and enzyme-substrate interactions (Sobrado et al, 2003). This N-terminal fragment, however, is required for being targeted by the ubiquitin-proteosome pathway (Gross-Mesilaty et al, 1997), which degrades proteins to small peptides (Ciechanover et al, 2000). So far crystal structures of TATs from Escherichia coli (Ko et al, 1999), T. cruzi (Blankenfeldt et al, 1999), and Homo sapiens (Protein Data Bank code, 3dyd) have been reported.…”

Section: Introductionmentioning

confidence: 99%

Tyrosine aminotransferase: biochemical and structural properties and molecular dynamics simulations

et al. 2010

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Tyrosine aminotransferase (TAT) catalyzes the transamination of tyrosine and other aromatic amino acids. The enzyme is thought to play a role in tyrosinemia type II, hepatitis and hepatic carcinoma recovery. The objective of this study is to investigate its biochemical and structural characteristics and substrate specificity in order to provide insight regarding its involvement in these diseases. Mouse TAT (mTAT) was cloned from a mouse cDNA library, and its recombinant protein was produced using Escherichia coli cells and purified using various chromatographic techniques. The recombinant mTAT is able to catalyze the transamination of tyrosine using α-ketoglutaric acid as an amino group acceptor at neutral pH. The enzyme also can use glutamate and phenylalanine as amino group donors and p-hydroxy-phenylpyruvate, phenylpyruvate and alpha-ketocaproic acid as amino group acceptors. Through macromolecular crystallography we have determined the mTAT crystal structure at 2.9 Å resolution. The crystal structure revealed the interaction between the pyridoxal-5′-phosphate cofactor and the enzyme, as well as the formation of a disulphide bond. The detection of disulphide bond provides some rational explanation regarding previously observed TAT inactivation under oxidative conditions and reactivation of the inactive TAT in the presence of a reducing agent. Molecular dynamics simulations using the crystal structures of Trypanosoma cruzi TAT and human TAT provided further insight regarding the substrate-enzyme interactions and substrate specificity. The biochemical and structural properties of TAT and the binding of its cofactor and the substrate may help in elucidation of the mechanism of TAT inhibition and activation.

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“…For example, this pathway regulates the processing of MHC class I-restricted antigens [Rock et al, 1994], and metabolic enzymes such as tyrosine amino transferase (TAT) and Cu/Zn superoxide dismutase [Hoffman et al, 1996;Gross-Mesilaty et al, 1997]. Several cell cycle protein substrates are also degraded by the proteasome including p21, p27, p53, and cyclins [Scheffner et al, 1990;Glotzer et al, 1991;Pagano et al, 1995].…”

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confidence: 99%

26S proteasome inhibition induces apoptosis and limits growth of human pancreatic cancer

Shah

Potter

McDade

et al. 2001

J of Cellular Biochemistry

244

138

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The 26S proteasome degrades proteins that regulate transcription factor activation, cell cycle progression, and apoptosis. In cancer, this may allow for uncontrolled cell division, promoting tumor growth, and spread. We examined whether selective inhibition of the 26S proteasome with PS-341, a dipeptide boronic acid analogue, would block proliferation and induce apoptosis in human pancreatic cancer. Proteasome inhibition significantly blocked mitogen (FCS) induced proliferation of BxPC3 human pancreatic cancer cells in vitro, while arresting cell cycle progression and inducing apoptosis by 24 h. Accumulation of p21(Cip1-Waf-1), a cyclin dependent kinase (CDK) inhibitor normally degraded by the 26S proteasome, occurred by 3 h and correlated with cell cycle arrest. When BxPC3 pancreatic cancer xenografts were established in athymic nu/nu mice, weekly administration of 1 mg/kg PS-341 significantly inhibited tumor growth. Both cellular apoptosis and p21(Cip1-Waf-1) protein levels were increased in PS-341 treated xenografts. Inhibition of tumor xenograft growth was greatest (89%) when PS-341 was combined with the tumoricidal agent CPT-11. Combined CPT-11/PS-341 therapy, but not single agent therapy, yielded highly apoptotic tumors, significantly inhibited tumor cell proliferation, and blocked NF-kappaB activation indicating this systemic therapy was effective at the cancer cell level. 26S proteasome inhibition may represent a new therapeutic approach against this highly resistant and lethal malignancy.

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Degradation of tyrosine aminotransferase (TAT) via the ubiquitin–proteasome pathway

Cited by 27 publications

References 20 publications

Growth suppression and cell death by pyridoxal is dependent on p53 in the human breast cancer cell line MCF-7

Growth suppression and cell death by pyridoxal is dependent on p53 in the human breast cancer cell line MCF-7

Tyrosine aminotransferase: biochemical and structural properties and molecular dynamics simulations

26S proteasome inhibition induces apoptosis and limits growth of human pancreatic cancer

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