LAPTM4B Membrane Protein Introduction

Introduction of LAPTM4B

LAPTM4B, Lysosomal-associated transmembrane protein 4B, is a protein that in humans is encoded by the LAPTM4B gene. LAPTM4B protein contains a lysosome localization motif and localizes on late endosomes and lysosomes. The expression level of LAPTM4B is relatively high in breast, liver, lung, ovarian, uterine, gastric cancers. It can be utilized to be a therapeutic target to prevent chemotherapy resistance or a marker to identify the patients who will not benefit from anthracyclines.

Basic Information of LAPTM4B
Protein Name Lysosomal-associated transmembrane protein 4B
Gene Name LAPTM4B
Aliases Lysosome-associated transmembrane protein 4-beta, PSEC0001
Organism Homo sapiens (Human)
UniProt ID Q86VI4
Transmembrane Times 4
Length (aa) 370

Function of LAPTM4B Membrane Protein

LAPTM4B contains a lysosome localization motif and localizes on late endosomes and lysosomes. It is required for optimal lysosomal functions. It can block EGF-stimulated EGFR intraluminal sorting and degradation, while the inhibition function can be reversed by binding with the phosphatidylinositol 4,5-bisphosphate. Also, it can recruit SLC3A2 and SLC7A5 (the Leu transporter) to the lysosome, then result in promoting entry of leucine and other essential amino acids (EAAs) into the lysosome which can stimulate activation of proton-transporting vacuolar (V)-ATPase protein pump (V-ATPase) and hence mTORC1 activation. In addition, it plays a role as a negative regulator of TGFB1 production in regulatory T cells, and can bind ceramide and facilitates its exit from late endosome in order to control cell death pathways. Some clinical reports have shown that LAPTM4B can be utilized as a therapeutic target to prevent chemotherapy resistance or a marker to identify the patients who will not benefit from anthracyclines.

mechanisms for LAPTM4B promoting cancer development Fig.1 mechanisms for LAPTM4B promoting cancer development (Meng, 2016)

Application of LAPTM4B Membrane Protein in Literature

  1. Zhou K., et al. A Ceramide-Regulated Element in the Late Endosomal Protein LAPTM4B Controls Amino Acid Transporter Interaction. ACS Cent Sci. 2018, 4(5):548-558. PubMed ID: 29806001

    This article demonstrates the mechanistic insights into how transmembrane proteins sense and respond to ceramide, and indicates that LAPTM4B controls amino acid transporter interaction.

  2. Rusz O., et al. LAPTM4B gene copy number gain is associated with inferior response to anthracycline-based chemotherapy in hormone receptor negative breast carcinomas. Cancer Chemother Pharmacol. 2018. PubMed ID: 29770955

    This article shows the possible role of the LAPTM4B gene in anthracycline resistance in HR- breast cancer and analyzing LAPTM4B copy number pattern may support future treatment decision.

  3. Ding H., et al. Association between LAPTM4B gene polymorphism and susceptibility to and prognosis of diffuse large B-cell lymphoma. Oncol Lett. 2018, 15(1):264-270. PubMed ID: 29387221

    This study suggests that genetic polymorphisms of LAPTM4B are not a risk factor for the development of DLBCL, but the LAPTM4B*2 allele may a better prognostic indicator in patients with IPI score 3-5 in DLBCL.

  4. Wang L., et al. The Transcription Factor AP4 Promotes Oncogenic Phenotypes and Cisplatin Resistance by Regulating LAPTM4B Expression. Mol Cancer Res. 2018, 16(5):857-868. PubMed ID: 29378908

    This article demonstrates that AP4 promotes cell growth, migration, invasion, and cisplatin resistance through upregulation of LAPTM4B expression, thus representing an attractive therapeutic target for breast cancer.

  5. Meng Y., et al. AP4 positively regulates LAPTM4B to promote hepatocellular carcinoma growth and metastasis, while reducing chemotherapy sensitivity. Mol Oncol. 2018, 12(3):373-390. PubMed ID: 29337428

    This article provides evidence of the expression and functional coupling between AP4 and LAPTM4B and sheds light on the regulation of LAPTM4B and its function in liver cancer.

LAPTM4B Preparation Options

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  1. Meng Y, et al. (2016). LAPTM4B: an oncogene in various solid tumors and its functions. Oncogene. 287(52):43972-83.

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