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Last update 08 May 2025

calsenilin

Last update 08 May 2025

Basic Info

Synonyms

A-type potassium channel modulatory protein 3, Calsenilin, CSEN

+ [6]

Introduction

Calcium-dependent transcriptional repressor that binds to the DRE element of genes including PDYN and FOS. Affinity for DNA is reduced upon binding to calcium and enhanced by binding to magnesium. Seems to be involved in nociception (By similarity). Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels, such as KCND2/Kv4.2 and KCND3/Kv4.3. Modulates channel expression at the cell membrane, gating characteristics, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner. May play a role in the regulation of PSEN2 proteolytic processing and apoptosis. Together with PSEN2 involved in modulation of amyloid-beta formation.

Drugs associated with calsenilin

IQM-266

Target

calsenilin

Mechanism

calsenilin modulators

Active Org.

Instituto de Química Médica

Originator Org.

Instituto de Química Médica

Active Indication

Alzheimer Disease

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with calsenilin

100 Translational Medicine associated with calsenilin

0 Patents (Medical) associated with calsenilin

435

Literatures (Medical) associated with calsenilin

01 Jun 2025·Life Science Alliance

DAF-18/PTEN protects LIN-35/Rb from CLP-1/CAPN-mediated cleavage to promote starvation resistance

Article

Author: Baugh, L Ryan ; Chen, Jingxian ; Chitrakar, Rojin

Starvation resistance is a fundamental trait with profound influence on fitness and disease risk. DAF-18, theCaenorhabditis elegansortholog of the tumor suppressor PTEN, promotes starvation resistance. PTEN is a dual phosphatase, and DAF-18 promotes starvation resistance as a lipid phosphatase by antagonizing insulin/IGF and PI3K signaling, activating the tumor suppressor DAF-16/FoxO. However, if or how DAF-18/PTEN protein-phosphatase activity promotes starvation resistance is unknown. Using genetic, genomic, bioinformatic, and biochemical approaches, we identified theC. elegansretinoblastoma/RB protein homolog, LIN-35/Rb, as a critical mediator of the effect of DAF-18/PTEN on starvation resistance. We show that DAF-18/PTEN protects LIN-35/Rb from cleavage by the μ-Calpain homolog CLP-1/CAPN, and that LIN-35/Rb together with the repressive DREAM complex promotes starvation resistance. We conclude that the tumor suppressors DAF-18/PTEN and LIN-35/Rb function in a linear pathway, with LIN-35/Rb and the rest of the DREAM complex functioning as a transcriptional effector of DAF-18/PTEN protein-phosphatase activity resulting in repression of germline gene expression. This work is significant for revealing a network of tumor suppressors that promote survival during cellular and developmental quiescence.

01 Apr 2025·The FEBS Journal

A non‐canonical role for the tyrosyl tRNA synthetase: YARS regulates senescence induction and escape and controls the transcription of LIN9

Article

Author: Maarouf, Amine ; Petit, Coralie ; Lelièvre, Eric ; Coquelet, Hugo ; Vidi, Pierre‐Alexandre ; Toutain, Bertrand ; Leman, Geraldine ; Guillon, Jordan ; Guette, Catherine ; Boissard, Alice ; Coqueret, Olivier ; Henry, Cécile

Senescence is a tumor suppressor mechanism triggered by oncogene expression and chemotherapy treatment. It orchestrates a definitive cessation of cell proliferation through the activation of the p53‐p21 and p16‐Rb pathways, coupled with the compaction of proliferative genes within heterochromatin regions. Some cancer cells have the ability to elude this proliferative arrest but the signaling pathways involved in circumventing senescence remain to be characterized. We have recently described that malignant cells capable of evading senescence have an increased expression of specific tRNAs, such as tRNA‐Leu‐CAA and tRNA‐Tyr‐GTA, alongside the activation of their corresponding tRNA ligases, namely LARS and YARS. We have previously shown that YARS promotes senescence escape by activating proliferation and cell cycle genes but its functions during this proliferative arrest remain largely unknown. In this study, we have continued to characterize the functions of YARS, describing non‐canonical transcriptional functions of the ligase. Our results show that YARS is present in the nucleus of proliferating and senescent cells and interacts with the Trim28 transcriptional regulator. Importantly, YARS binds to the LIN9 promoter, a critical member of the Dream complex responsible for regulating cell cycle gene transcription. The ligase facilitates the binding and the phosphorylation of the type II RNA polymerase and promotes the deposition of activating epigenetic marks on the LIN9 promoter. Consequently, during senescence escape, YARS activates LIN9 expression and both proteins are necessary to induce the proliferation of emergent cells. These results underscore unconventional transcriptional functions of YARS in activating LIN9 expression in proliferating cells and during senescence escape.

01 Feb 2025·iScience

A human-specific, concerted repression of microcephaly genes contributes to radiation-induced growth defects in cortical organoids

Article

Author: Baatout, Sarah ; Buset, Jasmine ; De Vos, Winnok H ; Janssen, Ann ; Quintens, Roel ; Puype, Hanne ; Vermeirssen, Vanessa ; Etlioglu, Emre ; Rajan, Nicholas ; Berden, Lisa ; Ribeiro, Jessica Honorato ; Mbouombouo Mfossa, André Claude

Prenatal radiation-induced DNA damage poses a significant threat to neurodevelopment, resulting in microcephaly which primarily affects the cerebral cortex. So far, mechanistic studies were done in rodents. Here, we leveraged human cortical organoids to model fetal corticogenesis. Organoids were X-irradiated with moderate or high doses at different time points. Irradiation caused a dose- and time-dependent reduction in organoid size, which was more prominent in younger organoids. This coincided with a delayed and attenuated DNA damage response (DDR) in older organoids. Besides the DDR, radiation induced premature differentiation of neural progenitor cells (NPCs). Our transcriptomic analysis demonstrated a concerted p53-E2F4/DREAM-dependent repression of primary microcephaly genes, which was independently confirmed in cultured human NPCs and neurons. This was a human-specific feature, as it was not observed in mouse embryonic brains or primary NPCs. Thus, human cortical organoids are an excellent model for DNA damage-induced microcephaly and to uncover potentially targetable human-specific pathways.

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calsenilin

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