Cytoplasmic linker protein 1 (CLIP1)

Cytoplasmic linker protein 1 (CLIP1), also known as CLIP-170, is a member of the microtubule-plus-end-tracking proteins (+TIPs) that plays a fundamental role in regulating microtubule dynamics and linking cellular organelles to the cytoskeleton (UniProt: P30622). It facilitates the initiation of microtubule growth and is essential for the recruitment of the dynein-dynactin complex to microtubule ends, which is critical for retrograde transport and cell migration (PubMed: 10531020). During mitosis, CLIP1 is required for stable kinetochore-microtubule attachments and proper spindle assembly, ensuring the high fidelity of chromosome segregation (PubMed: 15632202). In clinical oncology, CLIP1 is recognized as a significant fusion partner for the Anaplastic Lymphoma Kinase (ALK) gene; the resulting CLIP1-ALK fusion acts as an oncogenic driver in non-small cell lung cancer (NSCLC) and is a validated target for ALK tyrosine kinase inhibitors (PubMed: 29330158). Beyond cancer, germline mutations in the CLIP1 gene have been identified as a cause of autosomal recessive primary microcephaly, underscoring its vital role in brain development and neuronal proliferation (PubMed: 25944325). While CLIP1 is not typically the primary target of small molecules, its involvement in microtubule stability makes it a key factor in determining cellular sensitivity to microtubule-targeting agents like taxanes.

Other names

CLIP-170RestinRSNCLIP170Cytoplasmic linker protein 170 kDa

Inhibition of the tyrosine kinase activity of CLIP1-ALK fusion proteins to disrupt oncogenic signaling pathways.