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https://www.readbyqxmd.com/read/26475862/tumor-suppressor-lzap-suppresses-wnt-%C3%AE-catenin-signaling-to-promote-zebrafish-embryonic-ventral-cell-fates-via-the-suppression-of-inhibitory-phosphorylation-of-glycogen-synthase-kinase-3
#1
Kun-Yang Lin, Shih-Han Kao, Chun-Ming Lai, Ciao-Ting Chen, Chang-Yi Wu, Hwei-Jan Hsu, Wen-Der Wang
Wnt/β-catenin signaling controls various cell fates in metazoan development, and its dysregulation is often associated with cancer formation. However, regulations of this signaling pathway are not completely understood. Here, we report that Lzap, a tumor suppressor, controls nuclear translocation of β-catenin. In zebrafish embryos disruption of lzap increases the expression of chordin (chd), which encodes a bone morphogenetic protein (BMP) antagonist that is localized in prospective dorsal cells and promotes dorsal fates...
December 11, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/23839039/overexpression-of-a-novel-regulator-of-p120-catenin-nlbp-promotes-lung-adenocarcinoma-proliferation
#2
Chang Hee Kim, Hae-Seong Nam, Eun Hee Lee, Seung Hun Han, Hyun Jung Cho, Hee Jin Chung, Nam Soo Lee, Suk Jin Choi, Hojoong Kim, Jeong Seon Ryu, Junhye Kwon, Hongtae Kim
NLBP (novel LZAP-binding protein) was recently shown to function as a tumor suppressor capable of inhibiting the NFκB signaling pathway. NLBP is also known as a negative regulator of cell invasion, and its expression is reduced in several cancer cell lines that have little invasive activity. Although these phenomena suggest that NLBP may be a potential tumor suppressor, its role as a tumor suppressor in human lung cancer is not well established. In contrast to our expectation, NLBP was highly expressed in the early stage of lung adenocarcinoma tissues, and overexpression of NLBP promoted proliferation of H1299 lung adenocarcinoma cells...
August 1, 2013: Cell Cycle
https://www.readbyqxmd.com/read/23478299/caspase-mediated-cleavage-of-c53-lzap-protein-causes-abnormal-microtubule-bundling-and-rupture-of-the-nuclear-envelope
#3
Jianchun Wu, Hai Jiang, Shouqing Luo, Mingsheng Zhang, Yinghua Zhang, Fei Sun, Shuang Huang, Honglin Li
Apoptotic nucleus undergoes distinct morphological and biochemical changes including nuclear shrinkage, chromatin condensation and DNA fragmentation, which are attributed to caspase-mediated cleavage of several nuclear substrates such as lamins. As most of active caspases reside in the cytoplasm, disruption of the nuclear-cytoplasmic barrier is essential for caspases to reach their nuclear targets. The prevailing proposed mechanism is that the increase in the permeability of nuclear pores induced by caspases allows the caspases and other apoptotic factors to diffuse into the nucleus, thereby resulting in the nuclear destruction...
May 2013: Cell Research
https://www.readbyqxmd.com/read/23152784/transcriptional-regulation-of-the-ufm1-conjugation-system-in-response-to-disturbance-of-the-endoplasmic-reticulum-homeostasis-and-inhibition-of-vesicle-trafficking
#4
Yinghua Zhang, Mingsheng Zhang, Jianchun Wu, Guohua Lei, Honglin Li
Homeostasis of the endoplasmic reticulum (ER) is essential for normal cellular functions. Disturbance of this homeostasis causes ER stress and activates the Unfolded Protein Response (UPR). The Ufm1 conjugation system is a novel Ubiquitin-like (Ubl) system whose physiological target(s) and biological functions remain largely undefined. Genetic study has demonstrated that the Ufm1-activating enzyme Uba5 is indispensible for erythroid differentiation in mice, highlighting the importance of this novel system in animal development...
2012: PloS One
https://www.readbyqxmd.com/read/23028987/expression-of-tip-1-confers-radioresistance-of-malignant-glioma-cells
#5
Miaojun Han, Hailun Wang, Hua-Tang Zhang, Zhaozhong Han
BACKGROUND: Malignant gliomas represent one group of tumors that poorly respond to ionizing radiation (IR) alone or combined with chemotherapeutic agents because of the intrinsic or acquired resistance. In this study, TIP-1 was identified as one novel protein that confers resistance of glioma cells to IR. METHODOLOGY/PRINCIPAL FINDINGS: Meta-analysis indicated that high TIP-1 expression levels correlate with the poor prognosis of human malignant gliomas after radiotherapy...
2012: PloS One
https://www.readbyqxmd.com/read/22028922/identification-of-lzap-as-a-new-candidate-tumor-suppressor-in-hepatocellular-carcinoma
#6
Jing-jing Zhao, Ke Pan, Jian-jun Li, Yi-bing Chen, Ju-gao Chen, Lin Lv, Dan-dan Wang, Qiu-zhong Pan, Min-shan Chen, Jian-chuan Xia
BACKGROUND: LZAP was isolated as a binding protein of the Cdk5 activator p35. LZAP has been highly conserved during evolution and has been shown to function as a tumor suppressor in various cancers. This study aimed to investigate LZAP expression and its prognostic value in hepatocellular carcinoma (HCC). Meanwhile, the function of LZAP in hepatocarcinogenesis was further investigated in cell culture models and mouse models. METHODS: Real-time quantitative PCR, western blot and immunohistochemistry were used to explore LZAP expression in HCC cell lines and primary HCC clinical specimens...
2011: PloS One
https://www.readbyqxmd.com/read/21523853/tumor-suppressor-lzap-regulates-cell-cycle-progression-doming-and-zebrafish-epiboly
#7
Dan Liu, Wen-Der Wang, David B Melville, Yong I Cha, Zhirong Yin, Natalia Issaeva, Ela W Knapik, Wendell G Yarbrough
Initial stages of embryonic development rely on rapid, synchronized cell divisions of the fertilized egg followed by a set of morphogenetic movements collectively called epiboly and gastrulation. Lzap is a putative tumor suppressor whose expression is lost in 30% of head and neck squamous cell carcinomas. Lzap activities include regulation of cell cycle progression and response to therapeutic agents. Here, we explore developmental roles of the lzap gene during zebrafish morphogenesis. Lzap is highly conserved among vertebrates and is maternally deposited...
June 2011: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/21513441/physiologic-correlates-of-sleep-quality-in-severe-emphysema
#8
Samuel L Krachman, Wissam Chatila, Ubaldo J Martin, Irene Permut, Gilbert E D'Alonzo, John P Gaughan, Alice L Sternberg, David Ciccolella, Gerard J Criner
BACKGROUND: Sleep quality is poor in severe emphysema. We hypothesized that in addition to nocturnal oxygen desaturation, the severity of airflow obstruction and degree of thoracic hyperinflation are responsible. METHODS: Twenty-five patients (14 males, 64 ± 6 [ ± SD] yrs, BMI 24.7 ± 4.2 kg/m(2)) with severe emphysema (FEV(1) = 28 ± 8% predicted, TLC = 125 ± 14% predicted) were studied. Measurements included spirometry, lung volumes, arterial blood gas, length of the diaphragm's zone of apposition (LZAP) and a polysomnogram...
June 2011: COPD
https://www.readbyqxmd.com/read/21385901/overexpression-of-a-novel-activator-of-pak4-the-cdk5-kinase-associated-protein-cdk5rap3-promotes-hepatocellular-carcinoma-metastasis
#9
Grace Wing-Yan Mak, Mandy Man-Lok Chan, Veronica Yee-Law Leong, Joyce Man-Fong Lee, Tai-On Yau, Irene Oi-Lin Ng, Yick-Pang Ching
The CDK5 kinase regulatory subunit-associated protein 3 (CDK5RAP3 or C53/LZAP) regulates apoptosis induced by genotoxic stress. Although CDK5RAP3 has been implicated in cancer progression, its exact role in carcinogenesis is not well established. In this article, we report that CDK5RAP3 has an important prometastatic function in hepatocarcinogenesis. An examination of human hepatocellular carcinoma (HCC) samples revealed at least twofold overexpression of CDK5RAP3 transcripts in 58% (39/67) of HCC specimens when compared with corresponding nontumorous livers...
April 15, 2011: Cancer Research
https://www.readbyqxmd.com/read/21283629/lzap-inhibits-p38-mapk-p38-phosphorylation-and-activity-by-facilitating-p38-association-with-the-wild-type-p53-induced-phosphatase-1-wip1
#10
Hanbing An, Xinyuan Lu, Dan Liu, Wendell G Yarbrough
LZAP (Cdk5rap3, C53) is a putative tumor suppressor that inhibits RelA, Chk1 and Chk2 and activates p53. LZAP is lost in a portion of human head and neck squamous cell carcinoma and experimental loss of LZAP expression is associated with enhanced invasion, xenograft tumor growth and angiogenesis. p38 MAPK can increase or decrease proliferation and cell death depending on cellular context. LZAP has no known enzymatic activity, implying that its biological functions are likely mediated by its protein-protein interactions...
2011: PloS One
https://www.readbyqxmd.com/read/20228063/a-novel-c53-lzap-interacting-protein-regulates-stability-of-c53-lzap-and-ddrgk-domain-containing-protein-1-ddrgk1-and-modulates-nf-kappab-signaling
#11
Jianchun Wu, Guohua Lei, Mei Mei, Yi Tang, Honglin Li
C53/LZAP (also named as Cdk5rap3) is a putative tumor suppressor that plays important roles in multiple cell signaling pathways, including DNA damage response and NF-kappaB signaling. Yet how its function is regulated remains largely unclear. Here we report the isolation and characterization of two novel C53/LZAP-interacting proteins, RCAD (Regulator of C53/LZAP and DDRGK1) and DDRGK1 (DDRGK domain-containing protein 1). Our co-immunoprecipitation assays confirmed their interactions, while gel filtration assay indicated that C53/LZAP and RCAD may form a large protein complex...
May 14, 2010: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/20164180/a-novel-lzap-binding-protein-nlbp-inhibits-cell-invasion
#12
Junhye Kwon, Hyun Jung Cho, Seung Hun Han, Jin Gu No, Jae Young Kwon, Hongtae Kim
LXXLL/leucine zipper-containing alternative reading frame (ARF)-binding protein (LZAP) was recently shown to function as a tumor suppressor through inhibition of the NF-kappaB signaling pathway. LZAP is also known as a negative regulator of cell invasion, and its expression was demonstrated to be reduced in several tumor tissues. However, the molecular mechanism of the negative effect of LZAP on cell invasion is unclear. In this study, we identify NLBP as a novel LZAP-binding protein using tandem affinity purification...
April 16, 2010: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/19223857/tumor-suppressor-protein-c53-antagonizes-checkpoint-kinases-to-promote-cyclin-dependent-kinase-1-activation
#13
Hai Jiang, Jianchun Wu, Chen He, Wending Yang, Honglin Li
Cyclin-dependent kinase 1 (Cdk1)/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 (also known as Cdk5rap3 and LZAP) potentiates DNA damage-induced cell death by modulating the G2/M checkpoint. More recently, Wang et al. (2007) found that C53/LZAP may function as a tumor suppressor by way of inhibiting NF-kappaB signaling. We report here the identification of C53 protein as a novel regulator of Cdk1 activation...
April 2009: Cell Research
https://www.readbyqxmd.com/read/17785205/lzap-a-putative-tumor-suppressor-selectively-inhibits-nf-kappab
#14
Jialiang Wang, Hanbing An, Marty W Mayo, Albert S Baldwin, Wendell G Yarbrough
LZAP has been reported to inhibit cellular proliferation and clonogenic growth. Here, we report that decreased LZAP expression promoted cellular transformation, xenograft tumor growth, and xenograft tumor vascularity. Loss of LZAP also increased cellular invasion, and MMP-9 expression dependent on NF-kappaB. LZAP directly bound to RelA, impaired serine 536 phosphorylation of RelA, increased HDAC association with RelA, inhibited basal and stimulated NF-kappaB transcriptional activity, and was found at the promoter of selective NF-kappaB-responsive genes...
September 2007: Cancer Cell
https://www.readbyqxmd.com/read/16173922/a-novel-arf-binding-protein-lzap-alters-arf-regulation-of-hdm2
#15
Jialiang Wang, Xiaping He, Ying Luo, Wendell G Yarbrough
The tumour suppressor ARF (alternative reading frame) is encoded by the INK4a (inhibitor of cyclin-dependent kinase 4)/ARF locus, which is frequently altered in human tumours. ARF binds MDM2 (murine double minute 2) and releases p53 from inhibition by MDM2, resulting in stabilization, accumulation and activation of p53. Recently, ARF has been found to associate with other proteins, but, to date, little is known about ARF-associated proteins that are implicated in post-translational regulation of ARF activity...
January 15, 2006: Biochemical Journal
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