Rab1 in cell signaling, cancer and other diseases

Yang, Xia; Li, Xiao Xing; Zhang, Y. J.; Rodriguez-Rodriguez, L.; Xiang, Meng; Wang, Huiyun; Zheng, Xi

doi:10.1038/onc.2016.81

Cited by 84 publications

(61 citation statements)

References 73 publications

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“…We performed a similar analysis for the Golgi-resident Rab family GTPase, Ypt1, the essential Rab1 homolog that regulates ER-to-Golgi membrane trafficking by recruiting effectors to the membrane surfaces of ER-derived vesicles and the Golgi complex 33,34 . The primary guaninenucleotide exchange factor (GEF) that activates Ypt1 in vivo is the TRAPPIII complex 35,36 ; the related TRAPPII complex is also capable of promoting Ypt1 activation 37 .…”

Section: Events That Regulate Protein-protein Interactionsmentioning

confidence: 99%

In-depth and 3-Dimensional Exploration of the Budding Yeast Phosphoproteome

Lanz

Yugandhar

Gupta

et al. 2019

Preprint

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Phosphorylation is one of the most dynamic and widespread post-translational modifications regulating virtually every aspect of eukaryotic cell biology. Here we present a comprehensive phosphoproteomic dataset for budding yeast, comprised of over 30,000 high confidence phosphorylation sites identified by mass spectrometry. This single dataset nearly doubles the size of the known phosphoproteome in budding yeast and defines a set of cell cycle-regulated phosphorylation events. With the goal of enhancing the identification of functional phosphorylation events, we performed computational positioning of phosphorylation sites on available 3D protein structures and systematically identified events predicted to regulate protein complex architecture. Results reveal a large number of phosphorylation sites mapping to or near protein interaction interfaces, many of which result in steric or electrostatic "clashes" predicted to disrupt the interaction. Phosphorylation site mutants experimentally validate our predictions and support a role for phosphorylation in negatively regulating protein-protein interactions. With the advancement of Cryo-EM and the increasing number of available structures, our approach should help drive the functional and spatial exploration of the phosphoproteome.

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Section: Events That Regulate Protein-protein Interactionsmentioning

confidence: 99%

In-depth and 3-Dimensional Exploration of the Budding Yeast Phosphoproteome

Lanz

Yugandhar

Gupta

et al. 2019

Preprint

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“…These molecules function in many distinct and important cellular processes, including signal transduction in conjugation with the intracellular domain of transmembrane receptors, protein biosynthesis, cell cycle kinetics and differentiation, macroautophagy, vesicle transport, and protein translocation through membranes. [1][2][3][4][5] Abnormal GTPase activities are significant in the etiology of many human diseases. [6][7][8] In mammalian oocytes, many members of GTPase superfamily have been identified to be involved in meiosis progression.…”

Section: Introductionmentioning

confidence: 99%

GTPase-activating protein Elmod2 is essential for meiotic progression in mouse oocytes

Zhou

Shi

et al. 2017

Cell Cycle

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Meiotic failure in oocytes is the major determinant of human zygote-originated reproductive diseases, the successful accomplishment of meiosis largely relay on the normal functions of many female fertility factors. Elmod2 is a member of the Elmod family with the strongest GAP (GTPase-activating protein) activity; although it was identified as a possible maternal protein, its actual physiologic role in mammalian oocytes has not been elucidated. Herein we reported that among Elmod family proteins, Elmod2 is the most abundant in mouse oocytes, and that inhibition of Elmod2 by specific siRNA caused severe meiotic delay and abnormal chromosomal segregation during anaphase. Elmod2 knockdown also significantly decreased the rate of oocyte maturation (to MII, with first polar body extrusion), and significantly greater numbers of Elmod2-knockdown MII oocytes were aneuploid. Correspondingly, Elmod2 knockdown dramatically decreased fertilization rate. To investigate the mechanism(s) involved, we found that Elmod2 knockdown caused significantly more abnormal mitochondrial aggregation and diminished cellular ATP levels; and we also found that Elmod2 co-localized and interacted with Arl2, a GTPase that is known to maintain mitochondrial dynamics and ATP levels in oocytes. In summary, we found that Elmod2 is the GAP essential to meiosis progression of mouse oocytes, most likely by regulating mitochondrial dynamics.

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“…Rab1a represents an important therapeutic target as it has been implicated in the pathogenesis of several human diseases such as cardiomyopathy, Parkinson's disease and cancer. Rab1a regulates several cell-signaling pathways, such as mTOR and Notch [73][74][75]. A study identified Rab1a as an oncogene in colorectal carcinoma, promoting oncogenesis by direct interaction with mTORC1 resulting in hyper activation of the pathway [16].…”

Section: Regulation Of Apoptosis Through Production Of Intracellularmentioning

confidence: 99%

“…A study identified Rab1a as an oncogene in colorectal carcinoma, promoting oncogenesis by direct interaction with mTORC1 resulting in hyper activation of the pathway [16]. Beyond cancer, Rab1a proteins play a causal role in the pathogenesis of several human diseases such as cardiomyopathy and Parkinson's disease [73][74][75]. As a Golgi-localized Rab, regulating trafficking from the endoplasmic reticulum (ER) to the Golgi apparatus [75,76], Rab1a dysregulation induces apoptosis in cells through the induction of cellular stress.…”

Section: Regulation Of Apoptosis Through Production Of Intracellularmentioning

confidence: 99%

Rab GTPases: Emerging Oncogenes and Tumor Suppressive Regulators for the Editing of Survival Pathways in Cancer

Krishnan

Golden

Woodward

et al. 2020

Cancers

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The Rab GTPase family of proteins are mediators of membrane trafficking, conferring identity to the cell membranes. Recently, Rab and Rab-associated factors have been recognized as major regulators of the intracellular positioning and activity of signaling pathways regulating cell growth, survival and programmed cell death or apoptosis. Membrane trafficking mediated by Rab proteins is controlled by intracellular localization of Rab proteins, Rab-membrane interactions and GTP-activation processes. Aberrant expression of Rab proteins has been reported in multiple cancers such as lung, brain and breast malignancies. Mutations in Rab-coding genes and/or post-translational modifications in their protein products disrupt the cellular vesicle trafficking network modulating tumorigenic potential, cellular migration and metastatic behavior. Conversely, Rabs also act as tumor suppressive factors inducing apoptosis and inhibiting angiogenesis. Deconstructing the signaling mechanisms modulated by Rab proteins during apoptosis could unveil underlying molecular mechanisms that may be exploited therapeutically to selectively target malignant cells.

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Rab1 in cell signaling, cancer and other diseases

Cited by 84 publications

References 73 publications

In-depth and 3-Dimensional Exploration of the Budding Yeast Phosphoproteome

In-depth and 3-Dimensional Exploration of the Budding Yeast Phosphoproteome

GTPase-activating protein Elmod2 is essential for meiotic progression in mouse oocytes

Rab GTPases: Emerging Oncogenes and Tumor Suppressive Regulators for the Editing of Survival Pathways in Cancer

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