scholarly journals Rab25 in cancer: a brief update

2012 ◽  
Vol 40 (6) ◽  
pp. 1404-1408 ◽  
Author(s):  
Shreya Mitra ◽  
Kwai W. Cheng ◽  
Gordon B. Mills
Keyword(s):  
Cell Function ◽  
Critical Role ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Cellular Level ◽  
Endocytic Pathway ◽  
Rab Gtpase ◽  
Rab Gtpases ◽  
Cellular Polarity ◽  
Huge Impact

Derailed endocytosis is a hallmark of cancer. The endocytic pathway, as demonstrated by our laboratory, is a frequent target of genomic aberrations in cancer and plays a critical role in the maintenance of cellular polarity, stem cell function, bioenergetics, proliferation, motility, invasion, metastasis, apoptosis and autophagy. The Rab GTPases, along with their effectors, are critical regulators of this endocytic machinery and can have a huge impact on the cellular itinerary of growth and metabolism. Rab25 is an epithelial-cell-specific member of the Rab GTPase superfamily, sharing close homology with Rab11a, the endosomal recycling Rab GTPase. RAB25 has been implicated in various cancers, with reports presenting it as both an oncogene and a tumour-suppressor gene. At the cellular level, Rab25 was shown to contribute to invasiveness of cancer cells by regulating integrin trafficking. Recently, our laboratory uncovered a critical role for Rab25 in cellular energetics. Assimilating all of the existing evidence, in the present review, we give an updated overview of the complex and often context-dependent role of Rab25 in cancer.

scholarly journals Dlec1 is required for spermatogenesis and male fertility in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yu Okitsu ◽  
Mamoru Nagano ◽  
Takahiro Yamagata ◽  
Chizuru Ito ◽  
Kiyotaka Toshimori ◽  
...  
Keyword(s):  
Male Fertility ◽  
Primary Cilia ◽  
Critical Role ◽  
Intraflagellar Transport ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Adenocarcinoma Cells ◽  
Cilia Formation ◽  
Ring Complex

Abstract Deleted in lung and esophageal cancer 1 (DLEC1) is a tumour suppressor gene that is downregulated in various cancers in humans; however, the physiological and molecular functions of DLEC1 are still unclear. This study investigated the critical role of Dlec1 in spermatogenesis and male fertility in mice. Dlec1 was significantly expressed in testes, with dominant expression in germ cells. We disrupted Dlec1 in mice and analysed its function in spermatogenesis and male fertility. Dlec1 deletion caused male infertility due to impaired spermatogenesis. Spermatogenesis progressed normally to step 8 spermatids in Dlec1−/− mice, but in elongating spermatids, we observed head deformation, a shortened tail, and abnormal manchette organization. These phenotypes were similar to those of various intraflagellar transport (IFT)-associated gene-deficient sperm. In addition, DLEC1 interacted with tailless complex polypeptide 1 ring complex (TRiC) and Bardet–Biedl Syndrome (BBS) protein complex subunits, as well as α- and β-tubulin. DLEC1 expression also enhanced primary cilia formation and cilia length in A549 lung adenocarcinoma cells. These findings suggest that DLEC1 is a possible regulator of IFT and plays an essential role in sperm head and tail formation in mice.

Von Hippel–Lindau disease

2015 ◽  
Author(s):  
Thomas Connor ◽  
Patrick H. Maxwell
Keyword(s):  
Cellular Response ◽  
Familial Cancer ◽  
Critical Role ◽  
Clinical Manifestations ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Loss Of Function ◽  
Cancer Syndrome ◽  
Von Hippel Lindau ◽  
Vhl Disease

Von Hippel–Lindau (VHL) disease is a dominantly inherited familial cancer syndrome caused by germline mutations in the VHL tumour suppressor gene. The most frequent manifestations of VHL disease are retinal and central nervous system haemangioblastomas, clear cell renal cell carcinomas, and phaeochromocytomas. Genetic testing and active screening for clinical manifestations is now started in childhood and has greatly improved the prognosis for patients with VHL disease. The VHL protein plays a critical role in regulating the cellular response to changes in oxygen tension. Loss of VHL function results in constitutive activation of a range of angiogenic and metabolic pathways. New drug therapies have been developed that reverse some of the cellular consequences of VHL loss of function in kidney cancer.

scholarly journals Manipulation of Rab GTPase Function by Intracellular Bacterial Pathogens

2007 ◽  
Vol 71 (4) ◽  
pp. 636-652 ◽  
Author(s):  
John H. Brumell ◽  
Marci A. Scidmore
Keyword(s):  
Host Cell ◽  
Bacterial Pathogens ◽  
Endocytic Pathway ◽  
Host Cells ◽  
Eukaryotic Cells ◽  
Rab Gtpase ◽  
Host Immune System ◽  
Intracellular Pathogens ◽  
Cell Trafficking ◽  
Rab Gtpases

SUMMARY Intracellular bacterial pathogens have evolved highly specialized mechanisms to enter and survive within their eukaryotic hosts. In order to do this, bacterial pathogens need to avoid host cell degradation and obtain nutrients and biosynthetic precursors, as well as evade detection by the host immune system. To create an intracellular niche that is favorable for replication, some intracellular pathogens inhibit the maturation of the phagosome or exit the endocytic pathway by modifying the identity of their phagosome through the exploitation of host cell trafficking pathways. In eukaryotic cells, organelle identity is determined, in part, by the composition of active Rab GTPases on the membranes of each organelle. This review describes our current understanding of how selected bacterial pathogens regulate host trafficking pathways by the selective inclusion or retention of Rab GTPases on membranes of the vacuoles that they occupy in host cells during infection.

scholarly journals Contrasting patterns in the evolution of the Rab GTPase family in Archaeplastida

2014 ◽  
Vol 83 (4) ◽  
pp. 303-315 ◽  
Author(s):  
Romana Petrželková ◽  
Marek Eliáš
Keyword(s):  
Membrane Trafficking ◽  
Endocytic Pathway ◽  
Rab Gtpase ◽  
Rab Gtpases ◽  
Eukaryotic Diversity ◽  
Limited Sampling ◽  
Primary Plastid ◽  
Core Eudicots ◽  
Stem Lineage

Rab GTPases are a vast group of proteins serving a role of master regulators in membrane trafficking in eukaryotes. Previous studies delineated some 23 Rab and Rab-like paralogs ancestral for eukaryotes and mapped their current phylogenetic distribution, but the analyses relied on a limited sampling of the eukaryotic diversity. Taking advantage of the recent growth of genome and transcriptome resources for phylogenetically diverse plants and algae, we reanalyzed the evolution of the Rab family in eukaryotes with the primary plastid, collectively constituting the presumably monophyletic supergroup Archaeplastida. Our most important novel findings are as follows: (i) the ancestral set of Rabs in Archaeplastida included not only the paralogs Rab1, Rab2, Rab5, Rab6, Rab7, Rab8, Rab11, Rab18, Rab23, Rab24, Rab28, IFT27, and RTW (=Rabl2), as suggested previously, but also Rab14 and Rab34, because Rab14 exists in glaucophytes and Rab34 is present in glaucophytes and some green algae; (ii) except in embryophytes, Rab gene duplications have been rare in Archaeplastida. Most notable is the independent emergence of divergent, possibly functionally novel, in-paralogs of Rab1 and Rab11 in several archaeplastidial lineages; (iii) recurrent gene losses have been a significant factor shaping Rab gene complements in archaeplastidial species; for example, the Rab21 paralog was lost at least six times independently within Archaeplastida, once in the lineage leading to the “core” eudicots; (iv) while the glaucophyte <em>Cyanophora paradoxa</em> has retained the highest number of ancestral Rab paralogs among all archaeplastidial species studied so far, rhodophytes underwent an extreme reduction of the Rab gene set along their stem lineage, resulting in only six paralogs (Rab1, Rab2, Rab6, Rab7, Rab11, and Rab18) present in modern red algae. Especially notable is the absence of Rab5, a virtually universal paralog essential for the endocytic pathway, suggesting that endocytosis has been highly reduced or rewired in rhodophytes.

tumour suppressor gene and the tobacco industry

The Lancet ◽  
2005 ◽  
Vol 365 (9464) ◽  
pp. 1026-1027
Author(s):  
A BITTON ◽  
M NEUMAN ◽  
J BARNOYA ◽  
S GLANTZ
Keyword(s):  
Tobacco Industry ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor

scholarly journals RNA-binding proteins La and HuR cooperatively modulate translation repression of PDCD4 mRNA

2020 ◽  
pp. jbc.RA120.014894
Author(s):  
Ravi Kumar ◽  
Dipak Kumar Poria ◽  
Partho Sarothi Ray
Keyword(s):  
Inflammatory Response ◽  
Chronic Inflammation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Suppressor Gene ◽  
Cooperative Action ◽  
Translation Repression

Post-transcriptional regulation of gene expression plays a critical role in controlling the inflammatory response. An uncontrolled inflammatory response results in chronic inflammation, often leading to tumorigenesis. Programmed cell death 4 (PDCD4) is a pro-inflammatory tumor-suppressor gene which helps to prevent the transition from chronic inflammation to cancer. PDCD4 mRNA translation is regulated by an interplay between the oncogenic microRNA miR-21 and the RNA-binding protein (RBP) HuR in response to LPS stimulation, but the role of other regulatory factors remain unknown. Here we report that the RBP Lupus antigen (La) interacts with the 3’UTR of PDCD4 mRNA and prevents miR-21-mediated translation repression. While LPS causes nuclear-cytoplasmic translocation of HuR, it enhances cellular La expression. Remarkably, La and HuR were found to bind cooperatively to the PDCD4 mRNA and mitigate miR-21-mediated translation repression. The cooperative action of La and HuR reduced cell proliferation and enhanced apoptosis, reversing the pro-oncogenic function of miR-21. Together, these observations demonstrate a cooperative interplay between two RBPs, triggered differentially by the same stimulus, which exerts a synergistic effect on PDCD4 expression and thereby helps maintain a balance between inflammation and tumorigenesis.

FOXL2 in adult‐type granulosa cell tumour of the ovary: oncogene or tumour suppressor gene?

2021 ◽  
Author(s):  
Jessica A. Pilsworth ◽  
Anne‐Laure Todeschini ◽  
Samantha J. Neilson ◽  
Dawn R. Cochrane ◽  
Daniel Lai ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
Cell Tumour ◽  
Granulosa Cell Tumour ◽  
Adult Type

scholarly journals Paracellular and Transcellular Leukocytes Diapedesis Are Divergent but Interconnected Evolutionary Events

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 254
Author(s):  
Michel-Edwar Mickael ◽  
Norwin Kubick ◽  
Pavel Klimovich ◽  
Patrick Henckell Flournoy ◽  
Irmina Bieńkowska ◽  
...  
Keyword(s):  
Immune Cell ◽  
Critical Role ◽  
Cellular Polarity ◽  
Endothelial Layer ◽  
Trichoplax Adhaerens ◽  
Migration Pathway ◽  
Two Systems ◽  
Sequence Reconstruction ◽  
Rhoa Protein ◽  
Migration Pathways

Infiltration of the endothelial layer of the blood-brain barrier by leukocytes plays a critical role in health and disease. When passing through the endothelial layer during the diapedesis process lymphocytes can either follow a paracellular route or a transcellular one. There is a debate whether these two processes constitute one mechanism, or they form two evolutionary distinct migration pathways. We used artificial intelligence, phylogenetic analysis, HH search, ancestor sequence reconstruction to investigate further this intriguing question. We found that the two systems share several ancient components, such as RhoA protein that plays a critical role in controlling actin movement in both mechanisms. However, some of the key components differ between these two transmigration processes. CAV1 genes emerged during Trichoplax adhaerens, and it was only reported in transcellular process. Paracellular process is dependent on PECAM1. PECAM1 emerged from FASL5 during Zebrafish divergence. Lastly, both systems employ late divergent genes such as ICAM1 and VECAM1. Taken together, our results suggest that these two systems constitute two different mechanical sensing mechanisms of immune cell infiltrations of the brain, yet these two systems are connected. We postulate that the mechanical properties of the cellular polarity is the main driving force determining the migration pathway. Our analysis indicates that both systems coevolved with immune cells, evolving to a higher level of complexity in association with the evolution of the immune system.

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