Actin' up: RhoB in cancer and apoptosis

RhoB is a small GTPase that regulates actin organization and vesicle transport. It is required for signalling apoptosis in transformed cells that are exposed to farnesyltransferase inhibitors, DNA-damaging agents or taxol. Genetic analysis in mice indicates that RhoB is dispensable for normal cell physiology, but that it has a suppressor or negative modifier function in stress-associated processes, including cancer.

[1]  P. Armitage,et al.  A Two-stage Theory of Carcinogenesis in Relation to the Age Distribution of Human Cancer , 1957, British Journal of Cancer.

[2]  P. Nowell,et al.  A minute chromosome in human chronic granulocytic leukemia , 1960 .

[3]  A. Knudson Mutation and cancer: statistical study of retinoblastoma. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[4]  J. Rowley A New Consistent Chromosomal Abnormality in Chronic Myelogenous Leukaemia identified by Quinacrine Fluorescence and Giemsa Staining , 1973, Nature.

[5]  A. Knudson Mutation and Human Cancer , 1973 .

[6]  D. Comings A general theory of carcinogenesis. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[7]  W. W. Nichols,et al.  Chromosomal deletion and retinoblastoma. , 1976, The New England journal of medicine.

[8]  U. Francke,et al.  Sporadic bilateral retinoblastoma and 13q- chromosomal deletion. , 1976, Medical and pediatric oncology.

[9]  H. Varmus,et al.  DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA , 1976, Nature.

[10]  A. Knudson,et al.  Model for the incidence of embryonal cancers: application to retinoblastoma. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[11]  A. Knudson Retinoblastoma: a prototypic hereditary neoplasm. , 1978, Seminars in oncology.

[12]  R. Weinberg,et al.  Passage of phenotypes of chemically transformed cells via transfection of DNA and chromatin. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[13]  D. Lane,et al.  T antigen is bound to a host protein in SY40-transformed cells , 1979, Nature.

[14]  S. Moolgavkar,et al.  Two-event models for carcinogenesis: incidence curves for childhood and adult tumors☆ , 1979 .

[15]  S H Moolgavkar,et al.  Mutation and cancer: a model for human carcinogenesis. , 1981, Journal of the National Cancer Institute.

[16]  C. Croce,et al.  Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[17]  P. Leder,et al.  Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[18]  T. P. Dryja,et al.  Expression of recessive alleles by chromosomal mechanisms in retinoblastoma , 1983, Nature.

[19]  N. Heisterkamp,et al.  Evidence of a new chimeric bcr/c-abl mRNA in patients with chronic myelocytic leukemia and the Philadelphia chromosome. , 1985, The New England journal of medicine.

[20]  E. Canaani,et al.  Fused transcript of abl and bcr genes in chronic myelogenous leukaemia , 1985, Nature.

[21]  O. Witte,et al.  Cell lines and clinical isolates derived from Ph1-positive chronic myelogenous leukemia patients express c-abl proteins with a common structural alteration. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[22]  Stephen H. Friend,et al.  A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma , 1986, Nature.

[23]  A. Levine,et al.  The p53 proto-oncogene can act as a suppressor of transformation , 1989, Cell.

[24]  B. Vogelstein,et al.  A genetic model for colorectal tumorigenesis , 1990, Cell.

[25]  T. Hunter,et al.  The ras-related gene rhoB is an immediate-early gene inducible by v-Fps, epidermal growth factor, and platelet-derived growth factor in rat fibroblasts , 1991, Molecular and cellular biology.

[26]  L. Loeb,et al.  Mutator phenotype may be required for multistage carcinogenesis. , 1991, Cancer research.

[27]  P. Adamson,et al.  Intracellular localization of the P21rho proteins , 1992, The Journal of cell biology.

[28]  D. Housman,et al.  p53-dependent apoptosis modulates the cytotoxicity of anticancer agents , 1993, Cell.

[29]  M. Meuth,et al.  Mutator phenotypes in human colorectal carcinoma cell lines. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[30]  G. Prendergast,et al.  Farnesyltransferase inhibition causes morphological reversion of ras-transformed cells by a complex mechanism that involves regulation of the actin cytoskeleton , 1994, Molecular and cellular biology.

[31]  A. Kral,et al.  Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice , 1995, Nature Medicine.

[32]  B. Kaina,et al.  The Ras-related Small GTP-binding Protein RhoB Is Immediate-early Inducible by DNA Damaging Treatments (*) , 1995, The Journal of Biological Chemistry.

[33]  C. Der,et al.  Activation of Rac1, RhoA, and mitogen-activated protein kinases is required for Ras transformation , 1995, Molecular and cellular biology.

[34]  G. Prendergast,et al.  Evidence that farnesyltransferase inhibitors suppress Ras transformation by interfering with Rho activity , 1995, Molecular and cellular biology.

[35]  G. Prendergast,et al.  Critical role of Rho in cell transformation by oncogenic Ras. , 1995, Oncogene.

[36]  G. Zalcman,et al.  Regulation of Ras-related RhoB protein expression during the cell cycle. , 1995, Oncogene.

[37]  G. Woude,et al.  Abnormal Centrosome Amplification in the Absence of p53 , 1996, Science.

[38]  Jürg Zimmermann,et al.  Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr–Abl positive cells , 1996, Nature Medicine.

[39]  R. Muschel,et al.  The farnesyltransferase inhibitor FTI-277 radiosensitizes H-ras-transformed rat embryo fibroblasts. , 1996, Cancer research.

[40]  R. Bravo,et al.  Activation of the nuclear factor-kappaB by Rho, CDC42, and Rac-1 proteins. , 1997, Genes & development.

[41]  P. Casey,et al.  Farnesyltransferase Inhibitors Alter the Prenylation and Growth-stimulating Function of RhoB* , 1997, The Journal of Biological Chemistry.

[42]  L. Van Aelst,et al.  Rho GTPases and signaling networks. , 1997, Genes & development.

[43]  B. Calabretta,et al.  Transformation of hematopoietic cells by BCR/ABL requires activation of a PI‐3k/Akt‐dependent pathway , 1997, The EMBO journal.

[44]  S. Sebti,et al.  GGTI-298 induces G0-G1 block and apoptosis whereas FTI-277 causes G2-M enrichment in A549 cells. , 1997, Cancer research.

[45]  B. Kaina,et al.  rhoB Encoding a UV-inducible Ras-related Small GTP-binding Protein Is Regulated by GTPases of the Rho Family and Independent of JNK, ERK, and p38 MAP Kinase* , 1997, The Journal of Biological Chemistry.

[46]  C. Der,et al.  Farnesyltransferase inhibitors and cancer treatment: targeting simply Ras? , 1997, Biochimica et biophysica acta.

[47]  C. Nobes,et al.  PRK1 Is Targeted to Endosomes by the Small GTPase, RhoB* , 1998, The Journal of Biological Chemistry.

[48]  H. Moses,et al.  RhoB Is Stabilized by Transforming Growth Factor β and Antagonizes Transcriptional Activation* , 1998, The Journal of Biological Chemistry.

[49]  S. Narumiya,et al.  Overexpression of the rhoC gene correlates with progression of ductal adenocarcinoma of the pancreas. , 1998, British Journal of Cancer.

[50]  G. Prendergast,et al.  Non-Ras targets of farnesyltransferase inhibitors: focus on Rho , 1998, Oncogene.

[51]  G. Prendergast,et al.  Functional interaction between RhoB and the transcription factor DB1. , 1998, Cell adhesion and communication.

[52]  K. Kinzler,et al.  Genetic instabilities in human cancers , 1998, Nature.

[53]  R. Muschel,et al.  Inhibiting Ras prenylation increases the radiosensitivity of human tumor cell lines with activating mutations of ras oncogenes. , 1998, Cancer research.

[54]  T. Jessell,et al.  A role for rhoB in the delamination of neural crest cells from the dorsal neural tube. , 1998, Development.

[55]  R. Perona,et al.  Multiple Signalling Pathways Lead to the Activation of the Nuclear Factor κB by the Rho Family of GTPases* , 1998, The Journal of Biological Chemistry.

[56]  A. Casamayor,et al.  PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2 , 1999, Current Biology.

[57]  Ian Tomlinson,et al.  Selection, the mutation rate and cancer: Ensuring that the tail does not wag the dog , 1999, Nature medicine.

[58]  P. Samadder,et al.  Decreased sensitivity to 1-O-octadecyl-2-O-methyl-glycerophosphocholine in MCF-7 cells adapted for serum-free growth correlates with constitutive association of Raf-1 with cellular membranes. , 1999, Cancer research.

[59]  E K Rowinsky,et al.  Ras protein farnesyltransferase: A strategic target for anticancer therapeutic development. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[60]  G. Prendergast,et al.  Geranylgeranylated RhoB mediates suppression of human tumor cell growth by farnesyltransferase inhibitors. , 1999, Cancer research.

[61]  G. Prendergast,et al.  Cell Growth Inhibition by Farnesyltransferase Inhibitors Is Mediated by Gain of Geranylgeranylated RhoB , 1999, Molecular and Cellular Biology.

[62]  P. Parker,et al.  Regulation of epidermal growth factor receptor traffic by the small GTPase RhoB , 1999, Current Biology.

[63]  S. Merajver,et al.  A novel putative low-affinity insulin-like growth factor-binding protein, LIBC (lost in inflammatory breast cancer), and RhoC GTPase correlate with the inflammatory breast cancer phenotype. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[64]  G. Prendergast,et al.  Activation of the PI3'K-AKT pathway masks the proapoptotic effects of farnesyltransferase inhibitors. , 1999, Cancer research.

[65]  G. Prendergast,et al.  Targeting farnesyltransferase: is Ras relevant? , 1999, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[66]  S. Leach,et al.  K-Ras-independent effects of the farnesyl transferase inhibitor L-744,832 on cyclin B1/Cdc2 kinase activity, G2/M cell cycle progression and apoptosis in human pancreatic ductal adenocarcinoma cells. , 2000, Neoplasia.

[67]  T. Jessell,et al.  RhoB Alteration Is Necessary for Apoptotic and Antineoplastic Responses to Farnesyltransferase Inhibitors , 2000, Molecular and Cellular Biology.

[68]  S. Merajver,et al.  RhoC GTPase, a novel transforming oncogene for human mammary epithelial cells that partially recapitulates the inflammatory breast cancer phenotype. , 2000, Cancer research.

[69]  S. Sebti,et al.  Both Farnesylated and Geranylgeranylated RhoB Inhibit Malignant Transformation and Suppress Human Tumor Growth in Nude Mice* , 2000, The Journal of Biological Chemistry.

[70]  D. Coppola,et al.  The Phosphoinositide 3-OH Kinase/AKT2 Pathway as a Critical Target for Farnesyltransferase Inhibitor-Induced Apoptosis , 2000, Molecular and Cellular Biology.

[71]  B. Kaina,et al.  Ras-related GTPase RhoB forces alkylation-induced apoptotic cell death. , 2000, Biochemical and biophysical research communications.

[72]  G. Prendergast,et al.  Farnesyltransferase inhibitors: antineoplastic properties, mechanisms of action, and clinical prospects. , 2000, Seminars in cancer biology.

[73]  J. Erickson,et al.  The γ-subunit of the coatomer complex binds Cdc42 to mediate transformation , 2000, Nature.

[74]  Eric S. Lander,et al.  Genomic analysis of metastasis reveals an essential role for RhoC , 2000, Nature.

[75]  G. Prendergast,et al.  Geranylgeranylated RhoB is sufficient to mediate tissue‐specific suppression of Akt kinase activity by farnesyltransferase inhibitors , 2000, FEBS letters.

[76]  S. Sebti,et al.  Farnesyltransferase and geranylgeranyltransferase I inhibitors and cancer therapy: Lessons from mechanism and bench-to-bedside translational studies , 2000, Oncogene.

[77]  G. Prendergast,et al.  Farnesyltransferase inhibitors: antineoplastic mechanism and clinical prospects. , 2000, Current opinion in cell biology.

[78]  P. Parker,et al.  Rho GTPase Control of Protein Kinase C-related Protein Kinase Activation by 3-Phosphoinositide-dependent Protein Kinase* , 2000, The Journal of Biological Chemistry.

[79]  M. E. Perry,et al.  The p53 Tumor Suppressor Protein Does Not Regulate Expression of Its Own Inhibitor, MDM2, Except under Conditions of Stress , 2000, Molecular and Cellular Biology.

[80]  G. Prendergast Mode of action of farnesyltransferase inhibitors. , 2000, The Lancet. Oncology.

[81]  Kenji Nakamura,et al.  Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesis , 2000, Oncogene.

[82]  J. Millar,et al.  A MAP kinase-dependent actin checkpoint ensures proper spindle orientation in fission yeast , 2001, Nature.

[83]  David Michaelson,et al.  Differential Localization of Rho Gtpases in Live Cells , 2001, The Journal of cell biology.

[84]  B. Kaina,et al.  Transcriptional activation of the small GTPase gene rhoB by genotoxic stress is regulated via a CCAAT element. , 2001, Nucleic acids research.

[85]  B. Kaina,et al.  Rho GTPases Are Involved in the Regulation of NF-κB by Genotoxic Stress , 2001 .

[86]  B. Kaina,et al.  Ras-related GTPase RhoB Represses NF-κB Signaling* , 2001, The Journal of Biological Chemistry.

[87]  W. R. Bishop,et al.  The farnesyl transferase inhibitor SCH 66336 induces a G(2) --> M or G(1) pause in sensitive human tumor cell lines. , 2001, Experimental cell research.

[88]  G. Prendergast,et al.  RhoB Is Dispensable for Mouse Development, but It Modifies Susceptibility to Tumor Formation as Well as Cell Adhesion and Growth Factor Signaling in Transformed Cells , 2001, Molecular and Cellular Biology.

[89]  S. Sebti,et al.  The Farnesyltransferase Inhibitor, FTI-2153, Blocks Bipolar Spindle Formation and Chromosome Alignment and Causes Prometaphase Accumulation during Mitosis of Human Lung Cancer Cells* , 2001, The Journal of Biological Chemistry.

[90]  K. Hossmann,et al.  GTPase RhoB: An Early Predictor of Neuronal Death after Transient Focal Ischemia in Mice , 2001, Molecular and Cellular Neuroscience.

[91]  S. Narumiya,et al.  Localization of a mammalian homolog of diaphanous, mDia1, to the mitotic spindle in HeLa cells. , 2001, Journal of cell science.

[92]  G. Prendergast,et al.  RhoB is required to mediate apoptosis in neoplastically transformed cells after DNA damage , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[93]  A. Ridley Rho Proteins: Linking Signaling with Membrane Trafficking , 2001, Traffic.

[94]  S. Goodman,et al.  Evidence that genetic instability occurs at an early stage of colorectal tumorigenesis. , 2001, Cancer research.

[95]  A. Adjei,et al.  Blocking oncogenic Ras signaling for cancer therapy. , 2001, Journal of the National Cancer Institute.