LAPTM5

Official Full Name

lysosomal protein transmembrane 5

Organism

Homo sapiens

Gene ID

7805

Background

This gene encodes a transmembrane receptor that is associated with lysosomes. The encoded protein, also known as E3 protein, may play a role in hematopoiesis. [provided by RefSeq, Feb 2009]

Synonyms

CLAST6

Cat.No.	Product Name	Price
CSC-DC008546	Panoply™ Human LAPTM5 Knockdown Stable Cell Line	Inquiry
CSC-SC008546	Panoply™ Human LAPTM5 Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD09013Z	Human LAPTM5 adenoviral particles	Inquiry
LV16758L	human LAPTM5 (NM_006762) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH142265	shRNA set against Rat Laptm5(NM_053538.2)	Inquiry
SHH142283	shRNA set against Mouse Laptm5(NM_010686.3)	Inquiry
SHH328475	shRNA set against Human LAPTM5 (NM_006762.2)	Inquiry
SHH328479	shRNA set against Mouse LAPTM5 (NM_010686.3)	Inquiry
SHH328483	shRNA set against Rat LAPTM5 (NM_053538.2)	Inquiry

Cat.No.	Product Name	Price
CDFL006825	Mouse Laptm5 cDNA Clone(NM_010686.3)	Inquiry
CDFR013262	Rat Laptm5 cDNA Clone(NM_053538.2)	Inquiry
MiUTR1M-06524	LAPTM5 miRNA 3'UTR clone	Inquiry
MiUTR1R-02960	LAPTM5 miRNA 3'UTR clone	Inquiry
MiUTR3H-04141	LAPTM5 miRNA 3'UTR clone	Inquiry
CDCB188365	Rabbit LAPTM5 ORF clone (XM_002716064.2)	Inquiry
CDCL126189	Mouse LAPTM5 ORF clone (NM_006762.2)	Inquiry
CDCR249403	Mouse Laptm5 ORF Clone(NM_010686.3)	Inquiry
CDCR380309	Rat Laptm5 ORF Clone(NM_053538.2)	Inquiry
CDCS412898	Human LAPTM5 ORF Clone (BC106896)	Inquiry

Detailed Information

Recent Progress

During the process of introducing 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced differentiation of U937 cells into macrophages, human lysosomal-associated protein multi-spanning membrane 5 (LAPTM5) was identified by an ordered differential display-polymerase chain reaction (ODD-PCR) as an up-regulated cDNA fragment. LAPTM5 is a membrane protein that localizes to intracellular vesicles. It has been previously demonstrated that LAPTM5 expression level is decreased in neuroblastoma (NB) cells, and excessive accumulation of LAPTM5 was shown to induce lysosomal cell death in these cells. A series of research was conducted and it was found that LAPTM5 mRNA level is frequently decreased in various cancer cell lines. Furthermore, low expression in patients with esophageal squamous cell carcinoma (ESCC) and non-small cell lung cancer (NSCLC) was significantly correlated with poor prognosis. It was also shown that overexpression of LAPTM5 in several cancer cells induces lysosomal cell death due to lysosomal destabilization, indicated by leakage of lysosomal cathepsin D into the cytosol as well as impairment of autophagy. These findings suggested that the inactivation of LAPTM5 may contribute to tumorigenesis in a subset of human cancers.

In another research, transcriptome analysis revealed that in bladder cancer (BCa) tissues, there is a significant induction of LAPTM5. Transportation of LAPTM5 from Golgi complex to lysosome could be inhibited by deficiency of Nedd4, a key member of E3 ubiquitin ligase family. Therefore, it was hypothesized that LAPTM5 may be closely correlated with BCa tumorigenesis. In human BCa tissues, researchers observed that LAPTM5 was significantly induced at both mRNA and protein levels, consistent with the microarray result. Furthermore, BCa cell model with downregulated LAPTM5 revealed a significantly delayed growth rate in the BCa cells with knockdown of LAPTM5. Moreover, cell cycle at G0/G1 phase was triggered by decreased LAPTM5 as well, which could lead to delayed BCa cell growth. In contrast, no significant alteration of apoptosis in the BCa cells with downregulated LAPTM5 was observed. Further analysis showed significant reduced LAPTM5 suppressed cell metastasis. Furthermore, proteins involved in epithelial-mesenchymal transition (EMT) were strongly altered, playing a central role in metastasis. In addition, phosphorylated ERK1/2 and p38, which are key members of mitogen-activated protein kinase (MAPK) family regulating BCa tumorigenesis, were strongly decreased. These findings, taken together, suggested that decreased LAPTM5 inhibited proliferation and viability, as well as induced G0/G1 cell cycle arrest possibly via deactivation of ERK1/2 and p38 in BCa cells (Fig.1).

Fig. 1. LAPTM5 is strongly upregulated in BCa tissues compared with paracancerous tissues and normal bladder tissues. (Chen et al, 2017)

Autophagy, a lysosomal degradation pathway, is now emerging as an importance prosurvival or prodeath factor in response to some chemotherapy. In one previous study, it was found that the expression of LAPTM5 is closely related with acute lymphocytic leukemia. To investigate the association of LAPTM5 with autophagy, researchers overexpressed LAPTM5 in K562 cells, and the results showed LAPTM5 significantly decreased autophagy activity. Finally, the overexpression of LAPTM5 significantly reduced the pH value in lysosomal, which was very essential for autophagy-mediated degradation activity. Taken together, these results suggested that LAPTM5 decreased autophagy activity though downregulation of pH value in lysosomal. Therefore, LAPTM5 might represent a potential target modulating autophagy activity to increase sensitivity to chemotherapy in treatment of leukemia.

References:

Nuylan, M., Kawano, T., Inazawa, J., & Inoue, J. (2016). Down-regulation oflaptm5in human cancer cells. Oncotarget, 7(19), 28320-28328.
Kawai, Y., Ouchida, R., Yamasaki, S., Dragone, L., Tsubata, T., & Wang, J. Y. (2014). Laptm5 promotes lysosomal degradation of intracellular cd3 but not of cell surface cd3. Immunology & Cell Biology, 92(6), 527–534.
Chen, L., Wang, G., Luo, Y., Wang, Y., Xie, C., & Jiang, W., et al. (2017). Downregulation of laptm5 suppresses cell proliferation and viability inducing cell cycle arrest at g0/g1 phase of bladder cancer cells. International Journal of Oncology, 50(1), 263-271.
Jun, D. Y., Kim, H., Jang, W. Y., Lee, J. Y., Fukui, K., & Kim, Y. H. (2017). Ectopic overexpression of laptm5 results in lysosomal targeting and induces mcl-1 down-regulation, bak activation, and mitochondria-dependent apoptosis in human hela cells. Plos One, 12(5), e0176544.
Hu, S., Niu, Y. N., Wu, D., Hong, D., Wang, N. N., & Pan, J. (2014). Overexpression of lysosomal-associated protein transmembrane 5 (laptm5) deceases autophagy activity via reducing the lysosomal ph value. Blood, 124(21).

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