LIN54

Last update 08 May 2025

Basic Info

Synonyms

CXC domain-containing protein 1, CXCDC1, DKFZp686L1814

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Introduction

Component of the DREAM complex, a multiprotein complex that can both act as a transcription activator or repressor depending on the context (PubMed:17531812, PubMed:17671431). In G0 phase, the complex binds to more than 800 promoters and is required for repression of E2F target genes (PubMed:17531812, PubMed:17671431). In S phase, the complex selectively binds to the promoters of G2/M genes whose products are required for mitosis and participates in their cell cycle dependent activation (PubMed:17531812, PubMed:17671431). In the complex, acts as a DNA-binding protein that binds the promoter of CDK1 in a sequence-specific manner (PubMed:19725879). Specifically recognizes the consensus motif 5'-TTYRAA-3' in target DNA (PubMed:27465258).

100 Clinical Results associated with LIN54

100 Translational Medicine associated with LIN54

0 Patents (Medical) associated with LIN54

Literatures (Medical) associated with LIN54

01 Dec 2024·Histochemistry and Cell Biology

FOXM1 requires IDH1 for late genes expression in mitotic cells

Article

Author: Jain, Nishant ; Kancharana, Balabhaskararao ; Dutta, Hashnu

Isocitrate dehydrogenase 1 (IDH1) is a metabolic enzyme that converts isocitrate to α-ketoglutarate in cells. However, research on IDH1 is more focused on the metabolite D-2-hydroxyglutarate than the cellular roles of the IDH1 protein. Metabolic enzymes can moonlight by participating in diverse cellular processes in cancer cells. This moonlighting function of the metabolic enzymes can contribute to changes in gene expression. It is unknown whether IDH1 associates with any transcription factor. We asked whether IDH1 coordinates with forkhead box protein M1 (FOXM1) in mitotic cells to regulate late genes expression. We found that depletion of IDH1 reduces canonical FOXM1-target expression in mitotic cells. Also, IDH1 binds to FOXM1 and a subset of MuvB proteins, Lin-9 and Lin-54, in mitotic cells. Based on these observations, we suggest that IDH1 coordinates with FOXM1 in mitotic cells to regulate late genes expression.

30 Jun 2023·Journal of thoracic disease

Overexpressed FOXM1 collaborates with MMB to increase WEE1 inhibitor sensitivity in NSCLC.

Article

Author: Zhang, Weiqiang ; Zhao, Jing ; Tan, Jian ; Ma, Jingbo ; Liu, Keqiang

BackgroundNon-small cell lung cancer (NSCLC) is a common lung tumor with high mortality. The complex formed by MYB-MuvB complex (MMB) and forkhead box M1 (FOXM1) (MMB-FOXM1) plays a vital role in cell cycle progression to affect the progression of diseases. The role of the FOXM1-MMB complex in Wee1-like protein kinase (WEE1) inhibitor sensitivity in NSCLC keeps unclear.MethodsThe reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to measure the mRNA levels of FOXM1, LIN54, Replication Protein A (RPA), gammaH2AX (γH2AX) and Cyclin B (CCNB). The western blot was performed to examine the corresponding protein expressions. The Cell Counting Kit-8 (CCK-8) assay was performed to test cell survival.ResultIt was demonstrated that after AZD-1775 treatment, the decrease in cell survival mediated by FOXM1 overexpression (P<0.001) could be reversed by LIN54 knockdown (P<0.01) and that cell survival in the control group did not differ obviously from that in the pcDNA3.1-FOXM1+siLIN54 group, indicating that the FOXM1-MMB complex was necessary for WEE1 inhibitor sensitivity. Moreover, the mRNA and protein expression levels of RPA and γH2AX were increased after AZD-1775 treatment and FOXM1 overexpression (P<0.01), suggesting that FOXM1 upregulation enhanced DNA replication stress and DNA damage. Finally, we found that the increases in the mRNA and protein expression levels of CCNB mediated by FOXM1 (P<0.01) could be rescued by silencing LIN54 (P<0.001) and that CCNB expression in the control group did not differ obviously from that in the pcDNA3.1-FOXM1+siLIN54 group. These findings revealed that the FOXM1-MMB complex activated G2/M checkpoints. In our work, it was discovered that FOXM1 overexpression increased DNA replication stress, which increased DNA replication and pressure on the WEE1 checkpoint. On the other hand, FOXM1 can enhance CCNB expression, increase the threshold content of the CCNB/CDK1 complex, facilitate mitosis, and promote WEE1 dephosphorylation. Under these two conditions, sensitivity to the WEE1 inhibitor AZD-1775 is increased, which leads to the accumulation of DNA damage and drives the activation of apoptosis.ConclusionsOverexpressed FOXM1 collaborates with MMB to increase WEE1 inhibitor sensitivity in NSCLC. This discovery might highlight the regulatory function of FOXM1/MMB in the treatment of NSCLC patients.

01 Mar 2022·Journal of Biological ChemistryQ2 · BIOLOGY

The MuvB complex safeguards embryonic stem cell identity through regulation of the cell cycle machinery

Q2 · BIOLOGY

Article

Author: Wang, Jingnan ; Jiang, Qing ; Hao, Kunying ; Xu, Lijun ; Xia, Yin ; Qin, Jinzhong ; Dong, Lixia ; Wang, Congcong ; Zhao, Linchun

Increasing evidences indicate that unlimited capacity for self-renewal and pluripotency, two unique properties of embryonic stem cells (ESCs), are intrinsically linked to cell cycle control. However, the precise mechanisms coordinating cell fate decisions and cell cycle regulation remain to be fully explored. Here, using CRISPR/Cas9-mediated genome editing, we show that in ESCs, deficiency of components of the cell cycle regulatory MuvB complex Lin54 or Lin52, but not Lin9 or Lin37, triggers G2/M arrest, loss of pluripotency, and spontaneous differentiation. Further dissection of these phenotypes demonstrated that this cell cycle arrest is accompanied by the gradual activation of mesoendodermal lineage-specifying genes. Strikingly, the abnormalities observed in Lin54-null ESCs were partially but significantly rescued by ectopic coexpression of genes encoding G2/M proteins Cyclin B1 and Cdk1. Thus, our study provides new insights into the mechanisms by which the MuvB complex determines cell fate through regulation of the cell cycle machinery.

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