Characterization of LPTM4B: A Computational Approach
Paper Details
Characterization of LPTM4B: A Computational Approach
Abstract
Lysosomal-associated protein transmembrane-4 beta (LAPTM4B) is a putative novel oncogene. Elevated expression has been observed in many solid tumors as HCC, lung, breast, colon and ovarian cancer. The expression of LAPTM4B is also associated with MDR1 expression in solid tumors. Despite the importance of LAPTM4B in cancer progression and chemotherapy resistance, the structure of LAPTM4B is not known. The current study aimed to identify the three dimensional structure of LAPTM4B and its interactions with MDR1. Protscale server was used to predict the hydrophilicity, accessibility, polarity, flexibility, mutability, bulkiness and refractivity of LAPTM4B and results showed that it is a stable protein. There is no signal peptide in LAPTM4B as predicted through Signal Server. One acetylation site present in LAPTM4B at Ser3 as predicted through Net Acet. One O-linked glycosylation site present at position 62. According to Netphos 3.1 server predictions ten threonine phosphorylation sites, fourteen serine phosphorylation sites, four tyrosine specific phosphorylation sites might present in LAPTM4B. PKC and PKA are kinases do phosphorylation of LAPTM4B. Different physiological parameter of LAPTM4B was predicted trough Protparam server. Secondary structure showed that LAPTM4B is structured protein with alpha helices, coils and one beta sheet. Due to absence of any structural template, ab-initio modeling was used to predict three dimensional structure of LAPTM4B. The structure was stable and it may accord with the rule of stereochemistry. LAPTM4B was predicted to interact with ABCB1, PIK3R1 and so on. These results will help to understand protein structure and how it involved in multidrug resistance.
Altschul SF, Gish W, Miller W. 1995. Basic local alignment search tool. Journal of molecular biology 215(3), 403-410.
Cole C, Barber JD, Barton GJ. 2008. The Jpred 3 secondary structure prediction server. Nucleic acids research 36(suppl 2), W197-W201.
Garnier J, Gibrat JF, Robson B. 1996. GOR method for predicting protein secondary structure from amino acid sequence. Methods in enzymology 266, 540-553.
He J, Shao G, Zhou R. 2003. Effects of the novel gene, LAPTM4B, highly expression in hepatocellular carcinoma on cell proliferation and tumor genesis of NIH3T3 cells. Beijing Da Xue Xue Bao 35, 348-352.
Jones DT. 1999. Protein secondary structure prediction based on position-specific scoring matrices. Journal of molecular biology 292(2), 195-202.
Kasper G, Vogel A, Klaman I, Gröne J, Petersen I, Weber B, Castaños-Vélez E, Staub E, Mennerich D. 2005. The human LAPTM4b transcript is upregulated in various types of solid tumors and seems to play a dual functional role during tumor progression. Cancer Letter 224, 93-103.
Li L, Wei XH, Pan YP, Li HC, Yang H, He QH, Pang Y, Shan Y, Xiong FX, Shao GZ, Zhou RL. 2010. LAPTM4B: a novel cancer-associated gene motivates multidrug resistance through efflux and activating PI3K/AKT signaling. Oncogene 29, 5785-5795.
Li Y, Zou L, Li Q, Haibe-Kains B, Tian R, Li Y, Desmedt C, Sotiriou C, Szallasi Z, Iglehart JD, Richardson AL, Wang ZC. 2010. Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer. Natural Medicine 16, 214-218.
Liu X, Xiong F, Wei X, Yang H, Zhou R. 2009. LAPTM4B-35, a novel tetratransmembrane protein and its PPRP motif play critical roles in proliferation and metastatic potential of hepatocellular carcinoma cells. Cancer Science 100, 2335-2340.
Morris DG, Musat M, Czirják S, Hanzély Z, Lillington DM, Korbonits M, Grossman AB. 2005. Differential gene expression in pituitary adenomas by oligonucleotide array analysis. European Journal of Endocrinology 153, 143-51.
Shao GZ, Zhou RL, Zhang QY, Zhang Y, Liu JJ, Rui JA, Wei X, Ye DX. 2003. Molecular cloning and characterization of LAPTM4B, a novel gene unregulated in hepatocellular carcinoma. Oncogene 22, 5060-9.
Yang H, Xiong F, Wei X, Yang Y, McNutt MA, Zhou R. 2010. Overexpression of LAPTM4B-35 promotes growth and metastasis of hepatocellular carcinoma in vitro and in vivo. Cancer Letter 294, 236-244.
Zhou L, He XD, Chen J, Cui QC, Qu Q, Rui JA, Zhao YP. 2007. Overexpression of LAPTM4B-35 closely correlated with clinic pathological features and post-resectional survival of gallbladder carcinoma. European Journal of Cancer 43(4), 809-815.
Zhou L, He XD, Yu JC, Zhou RL, Yang H, Qu Q, Rui JA. 2010. Overexpression of LAPTM4B promotes growth of gallbladder carcinoma cells in vitro. American journal of Surgery 199, 515-521.
Zaira Rehman, Hajra Sadia, Ammad Fahim (2017), Characterization of LPTM4B: A Computational Approach; IJB, V10, N4, April, P295-301
https://innspub.net/characterization-of-lptm4b-a-computational-approach/
Copyright © 2017
By Authors and International
Network for Natural Sciences
(INNSPUB) https://innspub.net
This article is published under the terms of the
Creative Commons Attribution License 4.0