Structure-activity relationships in flexible protein domains: regulation of rho GTPases by RhoGDI and D4 GDI

Golovanov, Alexander P.; Chuang, Tsung Hsien; DerMardirossian, Céline; Barsukov, Igor; Hawkins, Dawn; Badii, Ramin; Bokoch, Gary M.; Lian, Lu; Roberts, G. C. K.

doi:10.1006/jmbi.2000.4262

Cited by 61 publications

(60 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the specificity of D4-GDI remains much less characterized (1,33,34). Although recombinant D4-GDI binds to purified Rac1, Cdc42, and RhoA, there is no evidence showing that they can form stable complexes in vivo.…”

Section: Discussionmentioning

confidence: 99%

D4-GDI, a Rho GTPase Regulator, Promotes Breast Cancer Cell Invasiveness

Zhang

2006

Cancer Research

View full text Add to dashboard Cite

D4-GDI is a Rho GDP dissociation inhibitor that is widely expressed in hematopoietic cells. Its possible expression and function in breast cancer cells has not been described. Here, we found that D4-GDI is expressed in a panel of breast cancer cell lines, but not in benign-derived mammary epithelial cells. Knockdown of D4-GDI expression in MDA-MB-231 cells by RNA interference blocks cell motility and invasion. The cells lacking D4-GDI grown on Matrigel revert to a normal breast epithelial phenotype characterized by the formation of cavitary structures. Silencing D4-GDI expression inhibits B1-integrin expression and cell-matrix adhesion. Reintroduction of D4-GDI fully restored both B1-integrin expression and cellular invasion. Knockdown of D4-GDI in BT549 cells results in a similar effect. These results show that D4-GDI modulates breast cancer cell invasive activities.

show abstract

Section: Discussionmentioning

confidence: 99%

D4-GDI, a Rho GTPase Regulator, Promotes Breast Cancer Cell Invasiveness

Zhang

2006

Cancer Research

View full text Add to dashboard Cite

show abstract

“…Some of these proteins and regions have been shown to contain partial or transient secondary and/or tertiary structural organization [29,30]. Our view is that the terms "unfolded" and "unstructured" would be misleading for these partially structured examples, and "flexible" has been used to describe structured regions with high B-factors rather than regions lacking structure, so herein and elsewhere we use the term intrinsically disordered protein (IDP) to cover the wide range of possibilities.…”

Section: Introductionmentioning

confidence: 99%

Predicting intrinsic disorder in proteins: an overview

et al. 2009

View full text Add to dashboard Cite

The discovery of intrinsically disordered proteins (IDP) (i.e., biologically active proteins that do not possess stable secondary and/or tertiary structures) came as an unexpected surprise, as the existence of such proteins is in contradiction to the traditional "sequence→structure→function" paradigm. Accurate prediction of a protein's predisposition to be intrinsically disordered is a necessary prerequisite for the further understanding of principles and mechanisms of protein folding and function, and is a key for the elaboration of a new structural and functional hierarchy of proteins. Therefore, prediction of IDPs has attracted the attention of many researchers, and a number of prediction tools have been developed. Predictions of disorder, in turn, are playing major roles in directing laboratory experiments that are leading to the discovery of ever more disordered proteins, and thereby leading to a positive feedback loop in the investigation of these proteins. In this review of algorithms for intrinsic disorder prediction, the basic concepts of various prediction methods for IDPs are summarized, the strengths and shortcomings of many of the methods are analyzed, and the difficulties and directions of future development of IDP prediction techniques are discussed.

show abstract

“…The Rho GDP dissociation inhibitor (RhoGDI) is a cellular regulatory protein that acts primarily by controlling the cellular distribution and activity of Rho GTPases (1)(2)(3)(4). It is a member of a family of GDIs that include RhoGDI (also known as RhoGDIa or RhoGDI-1), D4-GDI, and RhoGDI-3.…”

Section: Introductionmentioning

confidence: 99%

Rho GDP Dissociation Inhibitor Protects Cancer Cells against Drug-Induced Apoptosis

et al. 2005

View full text Add to dashboard Cite

Rho GDP dissociation inhibitor (RhoGDI) plays an essential role in control of a variety of cellular functions through interactions with Rho family GTPases, including Rac1, Cdc42, and RhoA. RhoGDI is frequently overexpressed in human tumors and chemoresistant cancer cell lines, raising the possibility that RhoGDI might play a role in the development of drug resistance in cancer cells. We found that overexpression of RhoGDI increased resistance of cancer cells (MDA-MB-231 human breast cancer cells and JLP-119 lymphoma cells) to the induction of apoptosis by two chemotherapeutic agents: etoposide and doxorubicin. Conversely, silencing of RhoGDI expression by DNA vector-mediated RNA interference (small interfering RNA) sensitized MDA-MB-231 cells to drug-induced apoptosis. Resistance to apoptosis was restored by reintroduction of RhoGDI protein expression. The mechanism for the antiapoptotic activity of RhoGDI may derive from its ability to inhibit caspasemediated cleavage of Rac1 GTPase, which is required for maximal apoptosis to occur in response to cytotoxic drugs. Taken together, the data show that RhoGDI is an antiapoptotic molecule that mediates cellular resistance to these chemotherapy agents. (Cancer Res 2005; 65(14): 6054-62)

show abstract

Structure-activity relationships in flexible protein domains: regulation of rho GTPases by RhoGDI and D4 GDI

Cited by 61 publications

References 51 publications

D4-GDI, a Rho GTPase Regulator, Promotes Breast Cancer Cell Invasiveness

D4-GDI, a Rho GTPase Regulator, Promotes Breast Cancer Cell Invasiveness

Predicting intrinsic disorder in proteins: an overview

Rho GDP Dissociation Inhibitor Protects Cancer Cells against Drug-Induced Apoptosis

Contact Info

Product

Resources

About