Ask about this productRelated genes to: HOOK3 antibody
- Gene:
- HOOK3 NIH gene
- Name:
- hook microtubule tethering protein 3
- Previous symbol:
- -
- Synonyms:
- HK3
- Chromosome:
- 8p11.21
- Locus Type:
- gene with protein product
- Date approved:
- 2003-11-25
- Date modifiied:
- 2016-07-14
Related products to: HOOK3 antibody
Related articles to: HOOK3 antibody
- Trastuzumab is frequently utilized to treat human epidermal growth factor receptor 2 (HER2)-positive breast cancer, though its effectiveness is frequently hindered by the development of chemotherapy resistance. Recent research has indicated that exosomes, serving as carriers for genetic material exchanged among diverse tumor cell populations, contribute to the transmission of drug resistance, thereby promoting cancer progression. However, the exact mechanisms through which exosomes originating from breast cancer influence drug resistance remain unclear. In this study, we performed sequencing on exosomes both before and after trastuzumab treatment. Our results demonstrated a significant reduction in miR-3529-3p levels in exosomes from breast cancer patients following trastuzumab treatment compared to pre-treatment levels. Furthermore, miR-3529-3p was also downregulated in cells resistant to trastuzumab. Notably, overexpressing miR-3529-3p counteracted trastuzumab resistance. Additionally, miR-3529-3p mitigated chemoresistance by inhibiting the Wnt signaling pathway through positively regulating HOOK3 expression. In summary, miR-3529-3p in exosomes plays a crucial role in overcoming trastuzumab resistance, highlighting its potential as both a therapeutic target and a prognostic marker for individuals with breast cancer. - Source: PubMed
Publication date: 2025/07/03
Zhu JunwenLu YingZhang Qingyuan - A deeper understanding of how teriparatide exerts its anabolic effects on bone tissue may open new avenues for osteoanabolic treatment. Our study aimed to identify long non-coding RNAs and messenger RNAs (mRNAs) regulated by teriparatide. Bone marrow mesenchymal stem cells (MSCs) were treated with teriparatide during osteogenic differentiation, and long RNA sequencing was performed. We identified 7 622 differentially expressed lncRNAs in both continuous and intermittent treatment groups compared to untreated MSCs. In intermittent treatment, the most upregulated lncRNAs were VCP, EMP1, OXA1L, LPP, and SCARB2, while in continuous treatment, they were XLOC_055533, SCARB2, HNRNPC, VCP, and CALM3. The most downregulated lncRNAs in intermittent treatment were KRTAP4-11, DUBR, MEG3, DIABLO, and ABI3BP, while in continuous treatment, they were XLOC_055164, SLC2A3, COPG1, and SMTN. Among mRNAs, the most upregulated in intermittent treatment were DNAJC25-GNG10, ZBTB4, SLC2A6, TMEM189-UBE2V1, and BDP1, whereas SLC2A6, ZBTB4, MX1, BDP1, and RSAD2 were the most upregulated in continuous treatment. The most downregulated mRNAs in intermittent treatment were PIP4K2B, GFI1B, ISY1-RAB43, AC010422.5, SESN2 and ISY1-RAB43, whereas ZDBF2, KLKB1, RPS10-NUDT3, and XLOC_055092 were the most downregulated mRNAs in continuous treatment. AC008622.2, MED17, and RNF213 emerged as the most critical lncRNAs for elucidating the mechanism of intermittent teriparatide therapy, while XLOC_055533, SPG7, and HOOK3 were highlighted as the most important lncRNAs in the continuous treatment. Additionally, we identified novel lncRNAs (KRTAP4-11, CEBPZOS, and CDC42SE2) that may have a role in teriparatide effects on MSCs. Identified lncRNAs and mRNAs could serve as therapeutic targets or diagnostic markers to improve osteoanabolic treatments. - Source: PubMed
Publication date: 2025/07/02
Vrščaj Lucija AnaMarc JanjaOstanek Barbara - Cytoplasmic dynein-1 (dynein) is the primary retrograde-directed microtubule motor in most eukaryotes. To be active, dynein must bind to the dynactin complex and a cargo-specific adaptor to form the . There are nearly 20 adaptors that, despite having low sequence identity, all contain two discrete domains that mediate binding to the same regions of dynein and dynactin. Additionally, all adaptors seem to generate active transport complexes with grossly similar structures. Despite these similarities, active transport complexes formed with different adaptors show differences in their velocity, run length, and microtubule binding affinity. The molecular features in adaptors that underlie the differences in activity is unknown. To address this question, we first generated a library of synthetic adaptors by deleting or systematically swapping characterized dynein and dynactin binding domains for four endogenous, model adaptors, NINL, BicD2, KASH5, and Hook3. We then used binding assays and TIRF-based motility assays to assess each synthetic adaptors' ability to bind and activate dynein and dynactin. First, we found that the adaptors' coiled-coil domains, which bind dynactin and the tail domain of dynein, are necessary and sufficient for dynein activation. Second, we found that all endogenous adaptors could be modified to yield a synthetic adaptor that formed more motile active transport complexes, which suggests that there is no selective pressure for adaptors to maximize dynein motility. Indeed, our data suggest that some endogenous adaptor sequences may have evolved to generate active transport complexes that are only moderately motile. Finally, we found that one synthetic adaptor was hyperactive and generated active transport complexes that moved faster, farther, and more frequently than all other endogenous and synthetic adaptors. By performing structure-function analyses with the hyperactive adaptor, we discovered that increased random coil at key positions in an adaptor sequence increases the likelihood that dynein-dynactin-adaptor complexes that assemble will be motile. Our work supports a model where increased adaptor flexibility facilitates a type of kinetic proofreading that specifically destabilizes improperly assembled and inactive dynein-dynactin-adaptor complexes. These results provide insight into how differences in adaptor sequences could contribute to differential dynein regulation. - Source: PubMed
Publication date: 2025/06/07
Siva AravinthaGillies John Pde Borchgrave AshleyGarrott Sharon RMishra RishiJbeily Rita ElClarke Reagan SConklin CameronGibson DaytanZang Juliana LDeSantis Morgan E - Microtubule-associated cargo transport, a central process governing the localization and movement of various cellular cargoes, is orchestrated by the coordination of two types of motor proteins (kinesins and dyneins), along with diverse adaptor and accessory proteins. Hook microtubule tethering protein 3 (Hook3) is a cargo adaptor that serves as a scaffold for recruiting kinesin family member 1C (KIF1C) and dynein, thereby regulating bidirectional cargo transport. Herein, we conduct structural and functional analyses of how Hook3 mediates KIF1C-dependent anterograde cargo transport through interaction with KIF1C and PTPN21. We verify the interactions among the three proteins and determine the crystal structure of the Hook3(553-624) - KIF1C(714-809) complex. Subsequent structure-based mutational analysis demonstrates that this complex formation is necessary and sufficient for the interaction between the full-length proteins in HEK293T cells and plays a key role in Hook3- and KIF1C-mediated anterograde transport in RPE1 cells. Thus, this study provides a basis for a comprehensive understanding of how Hook3 cooperates with other components during the initial steps of activation and assembly of the Hook3- and KIF1C-dependent cargo transport machinery. - Source: PubMed
Publication date: 2025/05/01
Lee Hye SeonYu DaseuliBaek Kyoung EunShin Ho-ChulKim Seung JunDo Heo WonKu Bonsu - Cellular cargos move bidirectionally on microtubules by recruiting opposite polarity motors dynein and kinesin. These motors show codependence, where one requires the activity of the other, although the mechanism is unknown. Here we show that kinesin-3 KIF1C acts as both an activator and a processivity factor for dynein, using in vitro reconstitutions of human proteins. Activation requires only a fragment of the KIF1C nonmotor stalk binding the cargo adapter HOOK3. The interaction site is separate from the constitutive factors FTS and FHIP, which link HOOK3 to small G-proteins on cargos. We provide a structural model for the autoinhibited FTS-HOOK3-FHIP1B (an FHF complex) and explain how KIF1C relieves it. Collectively, we explain codependency by revealing how mutual activation of dynein and kinesin occurs through their shared adapter. Many adapters bind both dynein and kinesins, suggesting this mechanism could be generalized to other bidirectional complexes. - Source: PubMed
Publication date: 2025/01/02
Abid Ali FerdosZwetsloot Alexander JStone Caroline EMorgan Tomos EWademan Richard FCarter Andrew PStraube Anne