A Unique Carboxyl-terminal Insert Domain in the Hematopoietic-specific, GTPase-deficient Rho GTPase RhoH Regulates Post-translational Processing

Troeger, Anja; Chae, Hee-Don; Şentürk, Mümine; Wood, Jenna; Williams, David A.

doi:10.1074/jbc.m113.505727

Cited by 12 publications

(9 citation statements)

References 54 publications

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“…We and others have demonstrated that RhoH acts as an adaptor protein associating with the Src-family protein tyrosine kinase Lck, c-Src tyrosine kinase Csk, and Syk-family protein tyrosine kinase Zap70 and Syk [ 6 – 8 ]. Because RhoH is anchored to the plasma membrane through myristoylation, it is able to recruit Lck, ZAP70, and Syk to the membrane to facilitate membrane proximal signal transduction [ 6 , 7 , 9 ]. Ligation of TCR by MHC/peptide complexes induces phosphorylation of TCR-ζ chain ITAMs by Lck, thereby initiating TCR-dependent signal transduction.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of RhoH Permits to Bypass the Pre-TCR Checkpoint

et al. 2015

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RhoH, an atypical small Rho-family GTPase, critically regulates thymocyte differentiation through the coordinated interaction with Lck and Zap70. Therefore, RhoH deficiency causes defective T cell development, leading to a paucity of mature T cells. Since there has been no gain-of-function study on RhoH before, we decided to take a transgenic approach to assess how the overexpression of RhoH affects the development of T cells. Although RhoH transgenic (RhoHtg) mice expressed three times more RhoH protein than wild-type mice, β-selection, positive, and negative selection in the thymus from RhoHtg mice were unaltered. However, transgenic introduction of RhoH into Rag2 deficient mice resulted in the generation of CD4+CD8+ (DP) thymocytes, indicating that overexpression of RhoH could bypass β-selection without TCRβ gene rearrangement. This was confirmed by the in vitro development of DP cells from Rag2-/-RhoHtg DN3 cells on TSt-4/Dll-1 stroma in an Lck dependent manner. Collectively, our results indicate that an excess amount of RhoH is able to initiate pre-TCR signaling in the absence of pre-TCR complexes.

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Section: Introductionmentioning

confidence: 99%

Overexpression of RhoH Permits to Bypass the Pre-TCR Checkpoint

et al. 2015

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“…Another gene, ENSG00000168421, is the tumor suppressor RHOH, a member of the Ras superfamily. Considering that this gene is expressed in hematopoietic cells, it is quite suitable for it to act as a liquid biopsy marker for the differential diagnosis of tumor [ 43 , 44 ]. Although this gene has been confirmed to contribute to tumorigenesis, there are few reports on it.…”

Section: Discussionmentioning

confidence: 99%

Identifying and analyzing different cancer subtypes using RNA-seq data of blood platelets

et al. 2017

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Detection and diagnosis of cancer are especially important for early prevention and effective treatments. Traditional methods of cancer detection are usually time-consuming and expensive. Liquid biopsy, a newly proposed noninvasive detection approach, can promote the accuracy and decrease the cost of detection according to a personalized expression profile. However, few studies have been performed to analyze this type of data, which can promote more effective methods for detection of different cancer subtypes. In this study, we applied some reliable machine learning algorithms to analyze data retrieved from patients who had one of six cancer subtypes (breast cancer, colorectal cancer, glioblastoma, hepatobiliary cancer, lung cancer and pancreatic cancer) as well as healthy persons. Quantitative gene expression profiles were used to encode each sample. Then, they were analyzed by the maximum relevance minimum redundancy method. Two feature lists were obtained in which genes were ranked rigorously. The incremental feature selection method was applied to the mRMR feature list to extract the optimal feature subset, which can be used in the support vector machine algorithm to determine the best performance for the detection of cancer subtypes and healthy controls. The ten-fold cross-validation for the constructed optimal classification model yielded an overall accuracy of 0.751. On the other hand, we extracted the top eighteen features (genes), including TTN, RHOH, RPS20, TRBC2, in another feature list, the MaxRel feature list, and performed a detailed analysis of them. The results indicated that these genes could be important biomarkers for discriminating different cancer subtypes and healthy controls.

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“…Rnd1, Rnd2, Rnd3, and RhoH/TTF represent a completely distinct group of proteins within the Rho family (Riou et al 2010;Troeger et al 2013), as they do not share several conserved and essential amino acids, including Gly-12 (Rac1 numbering) in the G1 motif (also called phosphate-binding loop or P-loop) and Gln-61 (Rac1 numbering) in the G3 motif or switch II region. The role of these residues in GTP hydrolysis is well described for Ras oncogene in human cancers (Chaps.…”

Section: Rho Family and The Molecular Switch Mechanismmentioning

confidence: 99%

Classical Rho Proteins: Biochemistry of Molecular Switch Function and Regulation

Zhang

Nouri

Amin

et al. 2014

Ras Superfamily Small G Proteins: Biology and Mechanisms 1

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Rho family proteins are involved in an array of cellular processes by modulating cytoskeletal organization, transcription, and cell cycle progression. The signaling functions of Rho family proteins are based on the formation of distinctive protein-protein complexes with their regulators and effectors. A necessary precondition for such differential interactions is an intact molecular switch function, which is a hallmark of most members of the Rho family. Such classical Rho proteins cycle between an inactive GDP-bound state and an active GTP-bound state. They specifically interact via a consensus-binding sites called switch I and II with three structurally and functionally unrelated classes of regulatory proteins, such as guanine nucleotide dissociation inhibitors (GDIs), guanine nucleotide exchange factors (GEFs), and GTPase-activating proteins (GAPs). Extensive studies in the last 25 years have provided invaluable insights into the molecular mechanisms underlying regulation and signal transduction of the Rho family proteins. In this chapter, we will review common features of Rho protein regulations and highlight specific aspects of their structure-function relationships. Keywords Effector • GAP • GDI • GEF • Rho GTPase • Switch region Abbreviations AAliphatic amino acid Bcr Breakpoint cluster region protein C Cysteine CZH CDM-zizimin homology

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A Unique Carboxyl-terminal Insert Domain in the Hematopoietic-specific, GTPase-deficient Rho GTPase RhoH Regulates Post-translational Processing

Cited by 12 publications

References 54 publications

Overexpression of RhoH Permits to Bypass the Pre-TCR Checkpoint

Overexpression of RhoH Permits to Bypass the Pre-TCR Checkpoint

Identifying and analyzing different cancer subtypes using RNA-seq data of blood platelets

Classical Rho Proteins: Biochemistry of Molecular Switch Function and Regulation

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