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Last update 23 Jan 2025

SKOR2

Last update 23 Jan 2025

Basic Info

Synonyms

CORL2, Functional Smad-suppressing element on chromosome 18, Fussel-18

+ [5]

Introduction

Exhibits transcriptional repressor activity (By similarity). Acts as a TGF-beta antagonist in the nervous system.

Drugs associated with SKOR2

WO2024258729

Patent Mining

Target

SKOR2

Mechanism-

Active Org.

Mayo Foundation for Medical Education & Research

Originator Org.

Mayo Foundation for Medical Education & Research

Active Indication

Nervous System Diseases

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with SKOR2

100 Translational Medicine associated with SKOR2

0 Patents (Medical) associated with SKOR2

Literatures (Medical) associated with SKOR2

01 Apr 2024·Development

Foxp and Skor family proteins control differentiation of Purkinje cells from Ptf1a- and Neurog1-expressing progenitors in zebrafish

Article

Author: Itoh, Tsubasa ; Shimizu, Takashi ; Hibi, Masahiko ; Nakanishi, Akiko ; Fujii, Yukimi ; Wang, Jui Chun ; Yura, Shinnosuke ; Uehara, Mari

ABSTRACTCerebellar neurons, such as GABAergic Purkinje cells (PCs), interneurons (INs) and glutamatergic granule cells (GCs) are differentiated from neural progenitors expressing proneural genes, including ptf1a, neurog1 and atoh1a/b/c. Studies in mammals previously suggested that these genes determine cerebellar neuron cell fate. However, our studies on ptf1a;neurog1 zebrafish mutants and lineage tracing of ptf1a-expressing progenitors have revealed that the ptf1a/neurog1-expressing progenitors can generate diverse cerebellar neurons, including PCs, INs and a subset of GCs in zebrafish. The precise mechanisms of how each cerebellar neuron type is specified remains elusive. We found that genes encoding the transcriptional regulators Foxp1b, Foxp4, Skor1b and Skor2, which are reportedly expressed in PCs, were absent in ptf1a;neurog1 mutants. foxp1b;foxp4 mutants showed a strong reduction in PCs, whereas skor1b;skor2 mutants completely lacked PCs, and displayed an increase in immature GCs. Misexpression of skor2 in GC progenitors expressing atoh1c suppressed GC fate. These data indicate that Foxp1b/4 and Skor1b/2 function as key transcriptional regulators in the initial step of PC differentiation from ptf1a/neurog1-expressing neural progenitors, and that Skor1b and Skor2 control PC differentiation by suppressing their differentiation into GCs.

01 Jan 2023·Frontiers in immunology

Identification of SKOR2 IgG as a novel biomarker of paraneoplastic neurologic syndrome.

Article

Author: Zekeridou, Anastasia ; McKeon, Andrew ; Rezk, Mohamed ; Dasari, Surendra ; Pittock, Sean J ; LaFrance-Corey, Reghann G ; Mills, John R ; Knight, Andrew M ; Dubey, Divyanshu ; Gupta, Pranjal ; Kapadia, Ronak K ; Guo, Yong

IntroductionThe development of new autoantigen discovery techniques, like programmable phage immunoprecipitation sequencing (PhIP-Seq), has accelerated the discovery of neural-specific autoantibodies. Herein, we report the identification of a novel biomarker for paraneoplastic neurologic syndrome (PNS), Sloan-Kettering-Virus-Family-Transcriptional-Corepressor-2 (SKOR2)-IgG, utilizing PhIP-Seq. We have also performed a thorough clinical validation using normal, healthy, and disease/cancer control samples.MethodsStored samples with unclassified staining at the junction of the Purkinje cell and the granule cell layers were analyzed by PhIP-Seq for putative autoantigen identification. The autoantigen was confirmed by recombinant antigen-expressing cell-based assay (CBA), Western blotting, and tissue immunofluorescence assay colocalization.ResultsPhIP-Seq data revealed SKOR2 as the candidate autoantigen. The target antigen was confirmed by a recombinant SKOR-2-expressing, and cell lysate Western blot. Furthermore, IgG from both patient samples colocalized with a commercial SKOR2-specific IgG on cryosections of the mouse brain. Both SKOR2 IgG-positive patients had central nervous system involvement, one presenting with encephalitis and seizures (Patient 1) and the other with cognitive dysfunction, spastic ataxia, dysarthria, dysphagia, and pseudobulbar affect (Patient 2). They had a refractory progressive course and were diagnosed with adenocarcinoma (Patient 1: lung, Patient 2: gallbladder). Sera from adenocarcinoma patients without PNS (n=30) tested for SKOR2-IgG were negative.DiscussionSKOR2 IgG represents a novel biomarker for PNS associated with adenocarcinoma. Identification of additional SKOR2 IgG-positive cases will help categorize the associated neurological phenotype and the risk of underlying malignancy.

15 Jul 2022·Development

Gata2, Nkx2-2 and Skor2 form a transcription factor network regulating development of a midbrain GABAergic neuron subtype with characteristics of REM-sleep regulatory neurons

Article

Author: Seja, Patricia ; Kilpinen, Sami ; Achim, Kaia ; Lelkes, Zoltan ; Stenberg, Tarja ; Kirjavainen, Anna ; Ono, Yuichi ; Singh, Parul ; Salminen, Marjo ; Makkonen, Aki ; Molchanova, Svetlana ; Lahti, Laura ; Partanen, Juha ; Aitta-Aho, Teemu

ABSTRACTThe midbrain reticular formation (MRF) is a mosaic of diverse GABAergic and glutamatergic neurons that have been associated with a variety of functions, including sleep regulation. However, the molecular characteristics and development of MRF neurons are poorly understood. As the transcription factor, Gata2 is required for the development of all GABAergic neurons derived from the embryonic mouse midbrain, we hypothesized that the genes expressed downstream of Gata2 could contribute to the diversification of GABAergic neuron subtypes in this brain region. Here, we show that Gata2 is required for the expression of several GABAergic lineage-specific transcription factors, including Nkx2-2 and Skor2, which are co-expressed in a restricted group of post-mitotic GABAergic precursors in the MRF. Both Gata2 and Nkx2-2 function is required for Skor2 expression in GABAergic precursors. In the adult mouse and rat midbrain, Nkx2-2-and Skor2-expressing GABAergic neurons locate at the boundary of the ventrolateral periaqueductal gray and the MRF, an area containing REM-off neurons regulating REM sleep. In addition to the characteristic localization, Skor2+ cells increase their activity upon REM-sleep inhibition, send projections to the dorsolateral pons, a region associated with sleep control, and are responsive to orexins, consistent with the known properties of midbrain REM-off neurons.

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SKOR2

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