更新于：2024-11-01

HASPIN

更新于：2024-11-01

基本信息

别名

germ cell associated 2 (haspin)、Germ cell-specific gene 2 protein、GSG2

+ [5]

简介

Serine/threonine-protein kinase that phosphorylates histone H3 at 'Thr-3' (H3T3ph) during mitosis. May act through H3T3ph to both position and modulate activation of AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle.

关联

项与 HASPIN 相关的药物

FM-301(Future Medicine)

靶点

HASPIN

作用机制

HASPIN抑制剂

在研机构

Future Medicine Co., Ltd.

原研机构

Future Medicine Co., Ltd.

在研适应症

胰腺癌

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

HSK-205

靶点

FLT3 x HASPIN

作用机制

FLT3抑制剂 [+1]

在研机构

Purdue University

原研机构

Purdue University

在研适应症

急性髓性白血病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

INDO-11M

靶点

HASPIN

作用机制

HASPIN抑制剂

在研机构

University of Salerno

原研机构

University of Salerno

在研适应症

肿瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 HASPIN 相关的临床结果

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100 项与 HASPIN 相关的转化医学

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0 项与 HASPIN 相关的专利（医药）

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195

项与 HASPIN 相关的文献（医药）

2024-12-31·Nucleus

Nuclear functions regulated by the VRK1 kinase

Review

作者: Lazo, Pedro A

In the nucleus, the VRK1 Ser-Thr kinase is distributed in nucleoplasm and chromatin, where it has different roles. VRK1 expression increases in response to mitogenic signals. VRK1 regulates cyclin D1 expression at G0 exit and facilitates chromosome condensation at the end of G2 and G2/M progression to mitosis. These effects are mediated by the phosphorylation of histone H3 at Thr3 by VRK1, and later in mitosis by haspin. VRK1 regulates the apigenetic patterns of histones in processes requiring chromating remodeling, such as transcription, replication and DNA repair. VRK1 is overexpressed in tumors, facilitating tumor progression and resistance to genotoxic treatments. VRK1 also regulates the organization of Cajal bodies assembled on coilin, which are necessary for the assembly of different types of RNP complexes. VRK1 pathogenic variants cuase defects in Cajal bodies, functionally altering neurons with long axons and leading to neurological diseases, such as amyotrophic laterla sclerosis, spinal muscular atrophy, distal hereditay motor neuropathies and Charcot-Marie-Tooth.

2024-10-29·Proceedings of the National Academy of Sciences

A protein phosphatase 1 specific phos phatase ta rgeting p eptide (PhosTAP) to identify the PP1 phosphatome

Article

作者: Choy, Meng S. ; Kettenbach, Arminja N. ; Nguyen, Hieu T. ; Page, Rebecca ; Kumar, Ganesan S. ; Peti, Wolfgang

Phosphoprotein phosphatases (PPPs) are the key serine/threonine phosphatases that regulate all essential signaling cascades. In particular, Protein Phosphatase 1 (PP1) dephosphorylates ~80% of all ser/thr phosphorylation sites. Here, we developed a phosphatase targeting peptide (PhosTAP) that binds all PP1 isoforms and does so with a stronger affinity than any other known PP1 regulator. This PhosTAP can be used as a PP1 recruitment tool for Phosphorylation Targeting Chimera (PhosTAC)-type recruitment in in vitro and cellular experiments, as well as in phosphoproteomics experiments to identify PP1-specific substrates and phosphosites. The latter is especially important to further our understanding of cellular signaling, as the identification of substrates and especially phosphosites that are targeted by specific phosphatases lags behind that of their kinase counterparts. Using PhosTAP-based proteomics, we show that, counter to our current understanding, many PP1 regulators are also substrates, that the number of residues between regulator PP1-binding and phosphosites vary significantly, and that PP1 counteracts the activities of mitotic kinases. Finally, we also found that Haspin kinase is a direct substrate of PP1 and that its PP1-dependent dephosphorylation modulates its activity during anaphase. Together, we show that PP1-specific PhosTAPs are a powerful tool for +studying PP1 activity in vitro and in cells.

2024-09-06·Science

Role of protein kinase PLK1 in the epigenetic maintenance of centromeres

Article

作者: Vetter, Ingrid R. ; Pesenti, Marion E. ; Pan, Dongqing ; Musacchio, Andrea ; Cmentowski, Verena ; Conti, Duccio ; Verza, Arianna Esposito

The centromere, a chromosome locus defined by the histone H3–like protein centromeric protein A (CENP-A), promotes assembly of the kinetochore to bind microtubules during cell division. Centromere maintenance requires CENP-A to be actively replenished by dedicated protein machinery in the early G 1 phase of the cell cycle to compensate for its dilution after DNA replication. Cyclin-dependent kinases (CDKs) limit CENP-A deposition to once per cell cycle and function as negative regulators outside of early G 1 . Antithetically, Polo-like kinase 1 (PLK1) promotes CENP-A deposition in early G 1 , but the molecular details of this process are still unknown. We reveal here a phosphorylation network that recruits PLK1 to the deposition machinery to control a conformational switch required for licensing the CENP-A deposition reaction. Our findings clarify how PLK1 contributes to the epigenetic maintenance of centromeres.