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Cited by 31Protein Kinase Regulation and GTPase SignalingCellular transport and secretionSphingolipid Metabolism and Signaling

The RAL Enigma: Distinct Roles of RALA and RALB in Cancer

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Richardson, Dillon S., Spehar, Jonathan M., Han, David T., Chakravarthy, Prathik A., Sizemore, Steven T.·2022·Cells
DOI 10.3390/cells11101645PMC PMC9139244
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Abstract

RALA and RALB are highly homologous small G proteins belonging to the RAS superfamily. Like other small GTPases, the RALs are molecular switches that can be toggled between inactive GDP-bound and active GTP-bound states to regulate diverse and critical cellular functions such as vesicle trafficking, filopodia formation, mitochondrial fission, and cytokinesis. The RAL paralogs are activated and inactivated by a shared set of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) and utilize similar sets of downstream effectors. In addition to their important roles in normal cell biology, the RALs are known to be critical mediators of cancer cell survival, invasion, migration, and metastasis. However, despite their substantial similarities, the RALs often display striking functional disparities in cancer. RALA and RALB can have redundant, unique, or even antagonistic functions depending on cancer type. The molecular basis for these discrepancies remains an important unanswered question in the field of cancer biology. In this review we examine the functions of the RAL paralogs in normal cellular physiology and cancer biology with special consideration provided to situations where the roles of RALA and RALB are non-redundant.

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  • RalA and RalB differ in their C-terminal hypervariable regions, which contribute to distinct post-translational modifications and subcellular localization patterns.

    “Despite this similarity, they differ in their C-terminal hypervariable regions, which contribute to distinct post-translational modifications and subcellular localization patterns 40 .”

    From Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover (2026) · cites this paper as [40]

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Cited by

Sorted by citations

Authors
Richardson, D. S., Spehar, J. M., Han, D. T., Chakravarthy, P. A., & Sizemore, S. T.
Affiliations
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US)
Corresponding author
Sizemore, Steven T.
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2022-05-14
Volume
11
Issue
10
Pages
1645
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells11101645
PMC
PMC9139244
OpenAlex
W4280582782
Cited by
31
References
5
Citations by year
2026: 12 · 2025: 7 · 2024: 8 · 2023: 4
FWCI
0.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
United States of America Department of Defense (W81XWH-20-1-0047)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
Keywords
RalA, RalB, Ras superfamily, cancer, guanine nucleotide exchange factor, GTPase-activating protein, tumor invasion, tumor cell migration, metastasis, molecular switches
MeSH terms
Cell Survival, Humans, Neoplasms, Monomeric GTP-Binding Proteins, GTPase-Activating Proteins, ral GTP-Binding Proteins

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