MAP4, or microtubule-associated protein 4, is a protein that plays significant roles in various cellular processes related to microtubules. Microtubules are key components of the cell's cytoskeleton, acting as "railways" for intracellular transport, and MAP4 is involved in regulating their functions. It may be associated with pathways like the innate immune response and intracellular trafficking. MAP4 is ubiquitously expressed and is thought to have a role in maintaining cellular functions related to organelle distribution [1,5].

In lung adenocarcinoma, high expression of MAP4 is associated with poorer overall survival. Down-regulation of MAP4 affects the migration and invasion of lung adenocarcinoma cells and participates in radiation resistance by mediating epithelial-mesenchymal transition (EMT) [2]. In ovarian cancer, MAP4 expression is significantly associated with histological subtype, stage, grade, and residual tumour, though no significant association with overall survival was found. It may be involved in early stages of tumour spread along with Syk and calpain-1 [3]. MAP4 also controls the dynein-dependent trafficking of BTN3A1, which is crucial for the TBK1-IRF3 signaling axis in the innate immune system. Depletion of MAP4 impairs cytosolic DNA-or RNA-mediated type I IFN responses [4]. In myoblasts, MAP4 promotes differentiation and autophagy, as miR-103-3p regulates these processes by targeting MAP4 [6].

In conclusion, MAP4 has diverse functions in cells, especially in relation to microtubule-related processes. Its study in various disease models, such as in lung and ovarian cancers, and in cellular processes like innate immunity and myoblast development, has provided insights into its role in disease progression and normal cellular functions. Understanding MAP4 can potentially offer new targets for cancer treatment, especially in improving radiosensitivity, and contribute to the understanding of cellular regulatory mechanisms.

References:

1. Goodson, Holly V, Jonasson, Erin M. 2018. Microtubules and Microtubule-Associated Proteins. In Cold Spring Harbor perspectives in biology, 10, . doi:10.1101/cshperspect.a022608. https://pubmed.ncbi.nlm.nih.gov/29858272/

2. Xia, Xiaochun, Ge, Yangyang, Ge, Fanghong, Li, Peng, Xu, Pengqin. 2024. MAP4 acts as an oncogene and prognostic marker and affects radioresistance by mediating epithelial-mesenchymal transition in lung adenocarcinoma. In Journal of cancer research and clinical oncology, 150, 88. doi:10.1007/s00432-024-05614-8. https://pubmed.ncbi.nlm.nih.gov/38341398/

3. Zhang, Siwei, Deen, Suha, Storr, Sarah J, Yao, Anqi, Martin, Stewart G. 2019. Expression of Syk and MAP4 proteins in ovarian cancer. In Journal of cancer research and clinical oncology, 145, 909-919. doi:10.1007/s00432-019-02856-9. https://pubmed.ncbi.nlm.nih.gov/30737623/

4. Seo, Minji, Lee, Seong-Ok, Kim, Ji-Hoon, Shin, Jinwook, Ahn, Kwangseog. 2016. MAP4-regulated dynein-dependent trafficking of BTN3A1 controls the TBK1-IRF3 signaling axis. In Proceedings of the National Academy of Sciences of the United States of America, 113, 14390-14395. doi:. https://pubmed.ncbi.nlm.nih.gov/27911820/

5. Nabti, Ibtissem, Reddy, Babu J N, Rezgui, Rachid, Gross, Steven P, Shubeita, George T. 2022. The ubiquitous microtubule-associated protein 4 (MAP4) controls organelle distribution by regulating the activity of the kinesin motor. In Proceedings of the National Academy of Sciences of the United States of America, 119, e2206677119. doi:10.1073/pnas.2206677119. https://pubmed.ncbi.nlm.nih.gov/36191197/

6. Zhang, Xianxian, Huang, Shihui, Niu, Xi, Wang, Jiafu, Ran, Xueqin. 2023. miR-103-3p Regulates the Differentiation and Autophagy of Myoblasts by Targeting MAP4. In International journal of molecular sciences, 24, . doi:10.3390/ijms24044130. https://pubmed.ncbi.nlm.nih.gov/36835542/