Developmentally regulated GTPases:: structure, function and roles in disease

Christian A E Westrip; Qinqin Zhuang; Charlotte Hall; Charlotte D Eaton; Mathew L Coleman

doi:10.1007/s00018-021-03961-0

Developmentally regulated GTPases: structure, function and roles in disease

Christian A E Westrip, Qinqin Zhuang, Charlotte Hall, Charlotte D Eaton, Mathew L Coleman

Research output: Contribution to journal › Review article › peer-review

125 Downloads (Pure)

Abstract

GTPases are a large superfamily of evolutionarily conserved proteins involved in a variety of fundamental cellular processes. The developmentally regulated GTP-binding protein (DRG) subfamily of GTPases consists of two highly conserved paralogs, DRG1 and DRG2, both of which have been implicated in the regulation of cell proliferation, translation and microtubules. Furthermore, DRG1 and 2 proteins both have a conserved binding partner, DRG family regulatory protein 1 and 2 (DFRP1 and DFRP2), respectively, that prevents them from being degraded. Similar to DRGs, the DFRP proteins have also been studied in the context of cell growth control and translation. Despite these proteins having been implicated in several fundamental cellular processes they remain relatively poorly characterized, however. In this review, we provide an overview of the structural biology and biochemistry of DRG GTPases and discuss current understanding of DRGs and DFRPs in normal physiology, as well as their emerging roles in diseases such as cancer.

Original language	English
Pages (from-to)	7219-7235
Number of pages	17
Journal	Cellular and Molecular Life Sciences
Volume	78
Issue number	23
DOIs	https://doi.org/10.1007/s00018-021-03961-0
Publication status	Published - 19 Oct 2021

Bibliographical note

Funding Information:
This work was funded by a CRUK programme Grant (C33483/A24552).

Funding Information:
This work was supported by Cancer Research UK. We apologize to those colleagues whose work we could not cite due to space constraints. We also thank all members of the Tumour Oxygenase Group for proof reading the manuscript and providing feedback.

Publisher Copyright:
© 2021, The Author(s).

Keywords

Translation
Ribosome
GTPase
Rbg1
Rbg2
Tma46
Gir2

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s00018-021-03961-0Licence: Creative Commons: Attribution (CC BY)

Westrip2021_Article_DevelopmentallyRegulatedGTPaseFinal published version, 2.77 MBLicence: Creative Commons: Attribution (CC BY)

Investigating the role of protein hydroxylation in cancer
Beggs, A., Stewart, G., Saponaro, M., Higgs, M. & Coleman, M.
Cancer Research Uk
1/11/17 → 31/03/25
Project: Research

Cite this

@article{6a212a95baa442f89ab7674a59ba0761,

title = "Developmentally regulated GTPases:: structure, function and roles in disease",

abstract = "GTPases are a large superfamily of evolutionarily conserved proteins involved in a variety of fundamental cellular processes. The developmentally regulated GTP-binding protein (DRG) subfamily of GTPases consists of two highly conserved paralogs, DRG1 and DRG2, both of which have been implicated in the regulation of cell proliferation, translation and microtubules. Furthermore, DRG1 and 2 proteins both have a conserved binding partner, DRG family regulatory protein 1 and 2 (DFRP1 and DFRP2), respectively, that prevents them from being degraded. Similar to DRGs, the DFRP proteins have also been studied in the context of cell growth control and translation. Despite these proteins having been implicated in several fundamental cellular processes they remain relatively poorly characterized, however. In this review, we provide an overview of the structural biology and biochemistry of DRG GTPases and discuss current understanding of DRGs and DFRPs in normal physiology, as well as their emerging roles in diseases such as cancer.",

keywords = "Translation, Ribosome, GTPase, Rbg1, Rbg2, Tma46, Gir2",

author = "Westrip, {Christian A E} and Qinqin Zhuang and Charlotte Hall and Eaton, {Charlotte D} and Coleman, {Mathew L}",

note = "Funding Information: This work was funded by a CRUK programme Grant (C33483/A24552). Funding Information: This work was supported by Cancer Research UK. We apologize to those colleagues whose work we could not cite due to space constraints. We also thank all members of the Tumour Oxygenase Group for proof reading the manuscript and providing feedback. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = oct,

day = "19",

doi = "10.1007/s00018-021-03961-0",

language = "English",

volume = "78",

pages = "7219--7235",

journal = "Cellular and Molecular Life Sciences",

issn = "1420-682X",

publisher = "Springer",

number = "23",

}

TY - JOUR

T1 - Developmentally regulated GTPases:

T2 - structure, function and roles in disease

AU - Westrip, Christian A E

AU - Zhuang, Qinqin

AU - Hall, Charlotte

AU - Eaton, Charlotte D

AU - Coleman, Mathew L

N1 - Funding Information: This work was funded by a CRUK programme Grant (C33483/A24552). Funding Information: This work was supported by Cancer Research UK. We apologize to those colleagues whose work we could not cite due to space constraints. We also thank all members of the Tumour Oxygenase Group for proof reading the manuscript and providing feedback. Publisher Copyright: © 2021, The Author(s).

PY - 2021/10/19

Y1 - 2021/10/19

N2 - GTPases are a large superfamily of evolutionarily conserved proteins involved in a variety of fundamental cellular processes. The developmentally regulated GTP-binding protein (DRG) subfamily of GTPases consists of two highly conserved paralogs, DRG1 and DRG2, both of which have been implicated in the regulation of cell proliferation, translation and microtubules. Furthermore, DRG1 and 2 proteins both have a conserved binding partner, DRG family regulatory protein 1 and 2 (DFRP1 and DFRP2), respectively, that prevents them from being degraded. Similar to DRGs, the DFRP proteins have also been studied in the context of cell growth control and translation. Despite these proteins having been implicated in several fundamental cellular processes they remain relatively poorly characterized, however. In this review, we provide an overview of the structural biology and biochemistry of DRG GTPases and discuss current understanding of DRGs and DFRPs in normal physiology, as well as their emerging roles in diseases such as cancer.

AB - GTPases are a large superfamily of evolutionarily conserved proteins involved in a variety of fundamental cellular processes. The developmentally regulated GTP-binding protein (DRG) subfamily of GTPases consists of two highly conserved paralogs, DRG1 and DRG2, both of which have been implicated in the regulation of cell proliferation, translation and microtubules. Furthermore, DRG1 and 2 proteins both have a conserved binding partner, DRG family regulatory protein 1 and 2 (DFRP1 and DFRP2), respectively, that prevents them from being degraded. Similar to DRGs, the DFRP proteins have also been studied in the context of cell growth control and translation. Despite these proteins having been implicated in several fundamental cellular processes they remain relatively poorly characterized, however. In this review, we provide an overview of the structural biology and biochemistry of DRG GTPases and discuss current understanding of DRGs and DFRPs in normal physiology, as well as their emerging roles in diseases such as cancer.

KW - Translation

KW - Ribosome

KW - GTPase

KW - Rbg1

KW - Rbg2

KW - Tma46

KW - Gir2

UR - http://www.scopus.com/inward/record.url?scp=85117225119&partnerID=8YFLogxK

U2 - 10.1007/s00018-021-03961-0

DO - 10.1007/s00018-021-03961-0

M3 - Review article

C2 - 34664086

SN - 1420-682X

VL - 78

SP - 7219

EP - 7235

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

IS - 23

ER -