Abstract
hTTLL12 is a member of the tubulin tyrosine ligase (TTL) family that is highly conserved in phylogeny. It has both SET-like and TTL-like domains, suggesting that it could have histone methylation and tubulin tyrosine ligase activities. Altered expression of hTTLL12 in human cells leads to specific changes in H4K20 trimethylation, and tubulin detyrosination, hTTLL12 does not catalyse histone methylation or tubulin tyrosination in vitro, as might be expected from the lack of critical amino acids in its SET-like and TTLL-like domains. hTTLL12 misexpression increases mitotic duration and chromosome numbers. These results suggest that hTTLL12 has non-catalytic functions related to tubulin and histone modification, which could be linked to its effects on mitosis and chromosome number stability.
Highlights
The human genome codes for may proteins that have not been assigned a validated function
We report its effects on histone and tubulin modifications, mitotic duration and chromosome numbers. hTTLL12 does not appear to have detectable in-vitro enzymatic activity related to the changes observed in cells
HTTLL12 appears to be an atypical member of the tubulin tyrosine ligase (TTL) protein family, from the presence of a SET-like domain, the loss of conserved residues found in other TTL family proteins, and the conservation of hTTLL12-specific features throughout many species
Summary
The human genome codes for may proteins that have not been assigned a validated function. In our screens of RNAs that are differentially expressed in tumours, we identified a number of encoded proteins with unknown functions that could potentially be targeted for therapeutic intervention [1]. We selected hTTLL12 for further study, since it has enzymic features. These results raise the possibility that hTTLL12 could contribute to tumorigenesis through effects on chromosome number stability [2]. In order to study whether hTTLL12 may have enzymatic activity, we used sequence homology searches to reveal the presence of SET-like and TTL-like domains in the N- and Cterminal parts of the molecule, respectively
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
