DOI: 10.1101/459669Nov 1, 2018Paper

Predicting JNK1 Inhibitors Regulating Autophagy in Cancer using Random Forest Classifier

BioRxiv : the Preprint Server for Biology
Chetna KumariMuhammad Abulaish

Abstract

Autophagy (in Greek: self-eating) is the cellular process for delivery of heterogenic intracellular material to lysosomal digestion. Protein kinases are integral to the autophagy process, and when dysregulated or mutated cause several human diseases. Atg1, the first autophagy-related protein identified is a serine/threonine protein kinases (STPKs). mTOR (mammalian Target of Rapamycin), AMPK (AMP-activated protein kinase), Akt, MAPK (mitogen-activated protein kinase) and PKC (protein kinase C) are other STPKs which regulate various components/steps of autophagy, and are often deregulated in cancer. MAPK have three subfamilies -- ERKs, p38, and JNKs. JNKs (c-Jun N-terminal Kinases) have three isoforms in mammals -- JNK1, JNK2, and JNK3, each with distinct cellular locations and functions. JNK1 plays role in starvation induced activation of autophagy, and the context-specific role of autophagy in tumorigenesis establish JNK1 a challenging anticancer drug target. Since JNKs are closely related to other members of MAPK family (p38, MAP kinase and the ERKs), it is difficult to design JNK-selective inhibitors. Designing JNK isoform-selective inhibitors are even more challenging as the ATP-binding sites among all JNKs are highly conser...Continue Reading

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