JNK-associated Leucine Zipper Protein Functions as a Docking Platform for Polo-like Kinase 1 and Regulation of the Associating Transcription Factor Forkhead Box Protein K1

Ramkumar, Poornima; Lee, Clement; Moradian, Annie; Sweredoski, Michael J.; Hess, Sonja; Sharrocks, Andrew D; Haines, Dale S.; Reddy, E. Premkumar

doi:10.1074/jbc.m115.664649

Cited by 10 publications

(13 citation statements)

References 48 publications

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“…This is also supported by the previous finding that JIP4, the 3.4 kbp splice variant of SPAG9 , has been characterized to be involved only in assembling p38MAPK-module but not that of JNK [10]. Although our present findings point to a role for JNK in JLP-mediated oncogenic signaling, it is possible that the other JLP-interacting proteins such as PLK1 can also have a significant role in JLP-promoted oncogenic signaling [46]. Further studies should define the interrelationship among these JLP-binding partners.…”

Section: Discussionsupporting

confidence: 91%

Aberrant expression of JNK-associated leucine-zipper protein, JLP, promotes accelerated growth of ovarian cancer

Yan

Gomathinayagam

et al. 2016

Oncotarget

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Ovarian cancer is the most fatal gynecologic cancer with poor prognosis. Etiological factors underlying ovarian cancer genesis and progression are poorly understood. Previously, we have shown that JNK-associated Leucine zipper Protein (JLP), promotes oncogenic signaling. Investigating the role of JLP in ovarian cancer, our present study indicates that JLP is overexpressed in ovarian cancer tissue and ovarian cancer cells. Transient overexpression of JLP promotes proliferation and invasive migration of ovarian cancer cells. In addition, ectopic expression of JLP confers long-term survival and clonogenic potential to normal fallopian tube-derived epithelial cells. Coimmunoprecipitation and colocalization analyses demonstrate the in vivo interaction of JLP and JNK, which is stimulated by lysophosphatidic acid (LPA), an oncogenic lipid growth factor in ovarian cancer. We also show that LPA stimulates the translocation of JLP-JNK complex to the perinuclear region of SKOV3-ip cells. JLP-knockdown using shRNA abrogates LPA-stimulated activation of JNK as well as LPA-stimulated proliferation and invasive migration of SKOV3-ip cells. Studies using ovarian cancer xenograft mouse model indicate that the mice bearing JLP-silenced xenografts exhibits reduced tumor volume. Analysis of the xenograft tumor tissues indicate a reduction in the levels of JLP, JNK, phosphorylated-JNK, c-Jun and phosphorylated-c-Jun in JLP-silenced xenografts, thereby correlating the attenuated JLP-JNK signaling node with suppressed tumor growth. Thus, our results identify a critical role for JLP-signaling axis in ovarian cancer and provide evidence that targeting this signaling node could provide a new avenue for therapy.

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Section: Discussionsupporting

confidence: 91%

Aberrant expression of JNK-associated leucine-zipper protein, JLP, promotes accelerated growth of ovarian cancer

Yan

Gomathinayagam

et al. 2016

Oncotarget

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“…JLP interacts with the Polo-box domain (PBD), but not the Polo-kinase domain (PKD) of PLK1 in HEK293T cells ( 27 ). To examine whether JLP directly interacts with PLK1, we performed an in vitro glutathione S -transferase (GST) pull-down assays using bacterial recombinant S-tagged JLP and GST-PLK1 proteins (wild-type, PKD, and PBD).…”

Section: Resultsmentioning

confidence: 99%

JLP-centrosome is essential for the microtubule-mediated nucleocytoplasmic transport induced by extracellular stimuli

et al. 2019

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“…Collectively, these findings have begun to broadly demonstrate the diversity of CT antigen function in human cancer. In many cases, these discoveries are based on large-scale functional genomic screens, proteomic analyses, or gene expression profiling [24, 35, 39, 43, 46, 51–53, 59, 67]. The utility of such approaches in identifying functional CT antigens speaks to the importance of unbiased, hypothesis-generating tools in revealing unanticipated players on the tumorigenic landscape.…”

Section: Ct Antigens Participate In Diverse Cellular Processes In Hummentioning

confidence: 99%

Emerging Contributions of Cancer/Testis Antigens to Neoplastic Behaviors

Gibbs

Whitehurst

2018

Trends in Cancer

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Tumors of nearly every origin activate the expression of genes which is otherwise restricted to gametogenic cells. These genes encode proteins termed cancer/testis (CT) antigens, since expression outside of their naturally immune-privileged site can evoke an immune response. Despite extensive efforts to exploit CT antigens as immunotherapeutic targets, investigation of whether these proteins participate in tumorigenic processes has lagged. Here, we discuss emerging evidence that demonstrates that CT antigens can confer a selective advantage to tumor cells by promoting oncogenic processes or permitting evasion of tumor-suppressive mechanisms. These advances indicate the inherent flexibility of tumor cell regulatory networks to engage aberrantly expressed proteins to promote neoplastic behaviors, which could ultimately present novel therapeutic entry points.

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JNK-associated Leucine Zipper Protein Functions as a Docking Platform for Polo-like Kinase 1 and Regulation of the Associating Transcription Factor Forkhead Box Protein K1

Cited by 10 publications

References 48 publications

Aberrant expression of JNK-associated leucine-zipper protein, JLP, promotes accelerated growth of ovarian cancer

Aberrant expression of JNK-associated leucine-zipper protein, JLP, promotes accelerated growth of ovarian cancer

JLP-centrosome is essential for the microtubule-mediated nucleocytoplasmic transport induced by extracellular stimuli

Emerging Contributions of Cancer/Testis Antigens to Neoplastic Behaviors

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