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Last update 08 May 2025

KATNIP

Last update 08 May 2025

Basic Info

Synonyms

JBTS26, katanin interacting protein, Katanin-interacting protein

+ [2]

Introduction

May influence the stability of microtubules (MT), possibly through interaction with the MT-severing katanin complex.

Drugs associated with KATNIP

KATNIP/Tubulin modulators(Fudan University)

Target

KATNIP x Tubulin

Mechanism

KATNIP modulators [+1]

Active Org.

Fudan University

Originator Org.

Fudan University

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with KATNIP

100 Translational Medicine associated with KATNIP

0 Patents (Medical) associated with KATNIP

304

Literatures (Medical) associated with KATNIP

01 Feb 2025·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

Fidgetin binds spastin to attenuate the microtubule-severing activity

Article

Author: Wu, Ronghua ; Dong, Zhangji ; Qiang, Liang ; Liu, Mei ; Ramakrishnan, Skandha ; Sun, Ying ; Lai, Xiaona

Microtubule-severing enzymes such as spastin, katanin, and fidgetin, characterized by their AAA ATPase domains, are pivotal in modulating microtubule dynamics and behavior across various cellular processes. While spastin and katanin are recognized for their predominant and robust severing of stable microtubules, thereby enhancing microtubule turnover, fidgetin exhibits comparatively weaker severing activity and selectively targets labile microtubules. The interplay among these enzymes and their mutual regulatory mechanisms remains inadequately understood. In this study, we elucidate the functional interaction between spastin and fidgetin, focusing on their roles in microtubule severing and neurite outgrowth. Our findings demonstrate that fidgetin serves as a negative regulator of spastin's severing activity. Co-expression assays revealed that fidgetin significantly attenuates spastin's severing efficiency, as confirmed by fluorescence-based microtubule polymerization assays and quantitative imaging of microtubule dynamics. Co-immunoprecipitation and Förster Resonance Energy Transfer (FRET) analyses further established a direct interaction between fidgetin and spastin, suggesting that fidgetin modulates spastin's activity through direct binding, possibly contributing to forming the hetero-hexmeric ring for their severing activities. Functionally, spastin overexpression in neuronal cells enhances neurite outgrowth, an effect that is suppressed upon co-expression with fidgetin, indicating that fidgetin counterbalances spastin's activity to regulate neurite extension. Therefore, this study uncovers a previously unrecognized mechanism by which fidgetin modulates spastin's function, providing critical insights into the intricate regulation of microtubule severing. These findings have significant implications for therapeutic strategies targeting microtubule-severing activities, particularly in neurodevelopmental and neurodegenerative disorders where microtubule dysregulation is a hallmark.

15 Oct 2024·Development

KATANIN-mediated microtubule severing is required for MTOC organisation and function in Marchantia polymorpha

Article

Author: Attrill, Sarah T ; Dolan, Liam

ABSTRACTMicrotubule organising centres (MTOCs) are sites of localised microtubule nucleation in eukaryotic cells. Regulation of microtubule dynamics often involves KATANIN (KTN): a microtubule severing enzyme that cuts microtubules to generate new negative ends, leading to catastrophic depolymerisation. In Arabidopsis thaliana, KTN is required for the organisation of microtubules in the cell cortex, preprophase band, mitotic spindle and phragmoplast. However, as angiosperms lack MTOCs, the role of KTN in MTOC formation has yet to be studied in plants. Two unique MTOCs – the polar organisers – form on opposing sides of the preprophase nucleus in liverworts. Here, we show that KTN-mediated microtubule depolymerisation regulates the number and organisation of polar organisers formed in Marchantia polymorpha. Mpktn mutants that lacked KTN function had supernumerary disorganised polar organisers compared with wild type. This was in addition to defects in the microtubule organisation in the cell cortex, preprophase band, mitotic spindle and phragmoplast. These data are consistent with the hypothesis that KTN-mediated microtubule dynamics are required for the de novo formation of MTOCs, a previously unreported function in plants.

25 Jul 2024·Journal of Medicinal Chemistry

Discovery of Novel Diaryl-Substituted Fused Heterocycles Targeting Katanin and Tubulin with Potent Antitumor and Antimultidrug Resistance Efficacy

Article

Author: Jiang, Fuhao ; Liang, Yuru ; Wang, Yang ; Yu, Min ; Ding, Kuiling

Disrupting microtubule dynamics has emerged as a promising strategy for cancer treatment. However, drug resistance remains a challenge hindering the development of microtubule-targeting agents. In this work, a novel class of diaryl substituted fused heterocycles were designed, synthesized, and evaluated, which were demonstrated as effective dual katanin and tubulin regulators with antitumor activity. Following three rounds of stepwise optimization, compound 21b, featuring a 3H-imidazo[4,5-b]pyridine core, displayed excellent targeting capabilities on katanin and tubulin, along with notable antiproliferative and antimetastatic effects. Mechanistic studies revealed that 21b disrupts the microtubule network in tumor cells, leading to G2/M cell cycle arrest and apoptosis induction. Importantly, 21b exhibited significant inhibition of tumor growth in MDA-MB-231 and A549/T xenograft tumor models without evident toxicity and side effects. In conclusion, compound 21b presents a novel mechanism for disrupting microtubule dynamics, warranting further investigation as a dual-targeted antitumor agent with potential antimultidrug resistance properties.

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KATNIP

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