Academic Journal
Structure-Guided Prediction of the Functional Impact of DCLK1 Mutations on Tumorigenesis.
| Title: | Structure-Guided Prediction of the Functional Impact of DCLK1 Mutations on Tumorigenesis. |
|---|---|
| Authors: | Carli, Annalisa L. E., Hardy, Joshua M., Hoblos, Hanadi, Ernst, Matthias, Lucet, Isabelle S., Buchert, Michael |
| Source: | Biomedicines; Mar2023, Vol. 11 Issue 3, p990, 20p |
| Abstract: | Doublecortin-like kinase 1 (DCLK1) is a functional serine/threonine (S/T)-kinase and a member of the doublecortin family of proteins which are characterized by their ability to bind to microtubules (MTs). DCLK1 is a proposed cancer driver gene, and its upregulation is associated with poor overall survival in several solid cancer types. However, how DCLK1 associates with MTs and how its kinase function contributes to pro-tumorigenic processes is poorly understood. This review builds on structural models to propose not only the specific functions of the domains but also attempts to predict the impact of individual somatic missense mutations on DCLK1 functions. Somatic missense mutations in DCLK1 are most frequently located within the N-terminal MT binding region and likely impact on the ability of DCLK1 to bind to αβ-tubulin and to polymerize and stabilize MTs. Moreover, the MT binding affinity of DCLK1 is negatively regulated by its auto-phosphorylation, and therefore mutations that affect kinase activity are predicted to indirectly alter MT dynamics. The emerging picture portrays DCLK1 as an MT-associated protein whose interactions with tubulin heterodimers and MTs are tightly controlled processes which, when disrupted, may confer pro-tumorigenic properties. [ABSTRACT FROM AUTHOR] |
| Subject Terms: | MISSENSE mutation, CANCER genes, NEOPLASTIC cell transformation, TUBULINS, STRUCTURAL models |
| Copyright of Biomedicines is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| ISSN: | 22279059 |
| DOI: | 10.3390/biomedicines11030990 |
| Database: | Complementary Index |
Availability