Disease relevance of TTL

• Subclone 22 lacked almost all of TTL including the gene for IE 118 and induced only the HSV-1 IE 110 [1].
• Reactions with TTL and KL1 antibodies were generally positive in the stellate cells of the follicular or acanthomatous ameloblastomas [2].
• Low expression of human tubulin tyrosine ligase and suppressed tubulin tyrosination/detyrosination cycle are associated with impaired neuronal differentiation in neuroblastomas with poor prognosis [3].

High impact information on TTL

• Tubulin tyrosine ligase: a shared fold with the glutathione synthetase ADP-forming family [4].
• These results indicate that tubulin tyrosination regulates microtubule interactions with CAP-Gly microtubule plus-end tracking proteins and provide explanations for the involvement of TTL in tumor progression and in neuronal organization [5].
• In TTL-null fibroblasts, tubulin detyrosination and CAP-Gly protein mislocalization correlate with defects in both spindle positioning during mitosis and cell morphology during interphase [5].
• In an RTBM1 neuroblastoma cell line, hTTL was increased after treating the cells with bone morphogenetic protein 2 (BMP2) or all-trans retinoic acid (RA), which induced neuronal differentiation [3].
• Tubulin tyrosine ligase catalyzes ligation of the tyrosine residue to the COOH terminus of the detyrosinated form of alpha-tubulin [3].

Biological context of TTL

• Phosphorylation of TTL is predicted to occur in a postulated Mg(++)/-ATP binding fold, leading to inhibition of Mg(++)/ATP binding and TTL mediated catalysis [6].
• These results suggest that the deregulated tubulin tyrosination/detyrosination cycle caused by decreased expression of hTTL is associated with inhibition of neuronal differentiation and enhancement of cell growth in the primary neuroblastomas with poor outcome [3].
• To understand the molecular and genetic bases of neuroblastoma, we have generated its cDNA libraries and identified a human ortholog of tubulin tyrosine ligase gene (hTTL/Nbla0660) as a differentially expressed gene at high levels in a favorable subset of the tumor [3].
• The TTL.6 gene is a member of the tubulin-tyrosine ligase (TTL) family involved in apoptosis and preferentially expressed in the testis [7].

Associations of TTL with chemical compounds

• In addition to D-alanine-D-alanine ligase, glutathione synthetase, biotin carboxylase, and carbamoyl phosphate synthetase, enzymes with known three-dimensional structures, the ATP-grasp domain is predicted in the ribosomal protein S6 modification enzyme (RimK), urea amidolyase, tubulin-tyrosine ligase, and three enzymes of purine biosynthesis [8].
• Restoration of the membrane excitability was achieved by perfusing the axon with a medium that contained purified tubulin-tyrosine ligase, tubulin, ATP, Mg2+, K+, cyclic AMP, and 300 K Protein [9].

Regulatory relationships of TTL

• Additionally, I propose that tumor cells that are resistant to the effects of TNF-alpha may be so because of suppressed levels of "tubulin tyrosine ligase," which is responsible for the posttranslational tyrosination of alpha-tubulin [10].

Other interactions of TTL

• In this paper, I present evidence suggesting that the cycle itself is under the hierarchical control of reversible phosphorylation and that PKC mediated phosphorylation of TTL inhibits its activity, thereby preventing tubulin tyrosination [6].
• Keratin expression was studied immunohistochemically in 27 ameloblastomas using polyclonal antibody against wide-spectrum keratins (TTL) and monoclonal antibodies against lower- and higher-molecular-weight keratins (PKK1 and KL1), respectively, to clarify the tumor differentiation [2].
• Three steps to cancer: how phosphorylation of tubulin, tubulin tyrosine ligase and P-glycoprotein may generate and sustain cancer [11].

Analytical, diagnostic and therapeutic context of TTL

• The Servo 300 was connected to the TTL with a standard ventilator circuit [12].
• Methods: The flow signal used to evaluate the Morgan spirometer was produced by a Vent-Aid TTL Training Test Lung. The flow of air from the test lung was directed in series through the Morgan's volume transducer and into the bell of a 9-L Collins water-sealed spirometer [13].
• In addition, we found frequently truncated PCR products of hTTL transcripts with aberrant splicing in tumors [14].

References