4.7 Article

Comparative Nucleotide-Dependent Interactome Analysis Reveals Shared and Differential Properties of KRas4a and KRas4b

Journal

ACS CENTRAL SCIENCE
Volume 4, Issue 1, Pages 71-80

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acscentsci.7b00440

Keywords

-

Funding

  1. NIH [1R01GM121540-01A1, SIG 1S10 OD017992-01, S10RR025502]

Ask authors/readers for more resources

The KRAS gene encodes two isoforms, KRas4a and KRas4b. Differences in the signaling functions of the two KRas proteins are poorly understood. Here we report the comparative and nucleotide-dependent interactomes of KRas4a and KRas4b. Many previously unknown interacting proteins were identified, with some interacting with both isoforms while others prefer only one. For example, v-ATPase a2 and eIF2Bd interact with only KRas4b. Consistent with the v-ATPase interaction, KRas4b has a significant lysosomal localization. Comparing WT and constitutively active G12D mutant KRas, we examined differences in the effector proteins of the KRas4a and KRas4b. Interestingly, KRas4a binds RAF1 stronger than KRas4b. Correspondingly, KRas4a can better promote ERK phosphorylation and anchorage-independent growth than KRas4b. The interactome data represent a useful resource to understand the differences between KRas4a and KRas4b and to discover new function or regulation for them. A similar proteomic approach would be useful for studying numerous other small GTPases. GRAPHICS

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Optics

Exceptional Photon Blockade: Engineering Photon Blockade with Chiral Exceptional Points

Ran Huang, S. K. Ozdemir, Jie-Qiao Liao, Fabrizio Minganti, Le-Man Kuang, Franco Nori, Hui Jing

Summary: This study demonstrates the emergence of single-photon blockade in a Kerr microring resonator due to EP-induced asymmetric coupling and nonlinearity-induced anharmonic energy-level spacing. By tuning the EP position, quantum correlations can be controlled, opening up opportunities for the fabrication and utilization of single-photon quantum EP devices.

LASER & PHOTONICS REVIEWS (2022)

Article Multidisciplinary Sciences

Asymmetric Laplace Distribution Models for Financial Data: VaR and CVaR

Huiting Jing, Yang Liu, Jinghua Zhao

Summary: In the field of financial risk measurement, the assumption of normalcy is often broken, and the Asymmetric Laplace distribution provides a better option for modeling financial data. This distribution reveals the properties of empirical financial data sets better than the normal model. Therefore, it is a simple, creative, and useful choice for calculating risk measures.

SYMMETRY-BASEL (2022)

Article Integrative & Complementary Medicine

Effectiveness of Quantitative Shear Wave Elastography for the Prediction of Axillary Lymph Node Metastasis

Yingying Cheng, Guofu Li, Hui Jing, Shasha Yuan, Lei Zhang, Wen Cheng

Summary: This study evaluated the effectiveness of quantitative shear wave elastography (SWE) to predict axillary lymph node metastasis in invasive breast cancer. The elasticity index (EI) of SWE was found to be closely associated with pathologic results. Joint use of SWE and B-mode ultrasound (BUS) showed great potential in predicting metastatic lymph nodes.

EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE (2022)

Article Construction & Building Technology

Influence of considering substructures on seismic performances of suspen-dome structure

Zetao Zhao, Xiongyan Li, Renjie Liu, Suduo Xue, Tifeng Liu, Qinxin Fan, Hui Jing, Majid Dezhkam

Summary: This study investigates the influence of substructures on the seismic performance of the suspen-dome structure. By replacing the complex concrete substructures with steel substructures in shaking table tests, the accurate and effective method is proposed. The results demonstrate that substructures have a significant impact on the seismic performance of the suspen-dome, highlighting the importance of considering them in the analysis and design stages.

PROCEEDINGS OF THE INSTITUTION OF CIVIL ENGINEERS-STRUCTURES AND BUILDINGS (2022)

Letter Chemistry, Physical

Reply to Comment on Binding Affinity Determines Substrate Specificity and Enables Discovery of substrates for N-Myristoyltransferases

Dan Su, Tatsiana Kosciuk, Hening Lin

Summary: This article concludes that binding affinity is crucial for in vivo substrate specificity and proposes a method to identify substrate proteins for enzymes by utilizing existing interactome data. The Reply aims to clarify important points in the original article.

ACS CATALYSIS (2022)

Article Biology

trim-21 promotes proteasomal degradation of CED-1 for apoptotic cell clearance in C. elegans

Lei Yuan, Peiyao Li, Huiru Jing, Qian Zheng, Hui Xiao

Summary: This study reveals a unique mechanism for maintaining appropriate levels of the phagocytic receptor CED-1, which is responsible for apoptotic cell clearance. The E3 ubiquitin ligase TRIM-21, along with other proteins, catalyzes the poly-ubiquitination of CED-1, leading to its degradation and maintaining its proper levels for effective cell corpse clearance.

ELIFE (2022)

Article Biochemistry & Molecular Biology

The Acyl-CoA Specificity of Human Lysine Acetyltransferase KAT2A

Ananya Anmangandla, Yuxiang Ren, Qin Fu, Sheng Zhang, Hening Lin

Summary: Protein post-translational modifications play a vital role in regulating cellular functions. KAT2A, an important acetyltransferase, has been shown to have activity with various substrates, but acetylation remains its most efficient activity.

BIOCHEMISTRY (2022)

Article Multidisciplinary Sciences

IGF2BP2 promotes cancer progression by degrading the RNA transcript encoding a v-ATPase subunit

Arash Latifkar, Fangyu Wang, James J. Mullmann, Elena Panizza, Irma R. Fernandez, Lu Ling, Andrew D. Miller, Claudia Fischbach, Robert S. Weiss, Hening Lin, Richard A. Cerione, Marc A. Antonyak

Summary: This study reveals a previously unknown role for IGF2BP2 in mediating the degradation of a messenger RNA transcript essential for lysosomal function, which has significant biological and disease consequences.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

Article Biochemistry & Molecular Biology

Astrocyte Elevated Gene-1 Cys75 S-Palmitoylation by ZDHHC6 Regulates Its Biological Activity

Garrison Komaniecki, Maria Del Carmen Camarena, Eric Gelsleichter, Rachel Mendoza, Mark Subler, Jolene J. Windle, Mikhail G. Dozmorov, Zhao Lai, Devanand Sarkar, Hening Lin

Summary: Nonalcoholic fatty liver disease is a major risk factor for hepatocellular carcinoma and involves lipid accumulation, inflammation, and tumorigenesis. This study discovered that AEG-1 is palmitoylated at residue cysteine 75 (Cys75) and that mutation of Cys75 to serine (Ser) abolishes this palmitoylation. Further experiments in mice revealed that the Cys75 mutation activates signaling pathways related to cell proliferation, motility, inflammation, angiogenesis, and lipid accumulation in hepatocytes. This finding suggests that palmitoylation restricts the oncogenic and NASH-promoting functions of AEG-1.

BIOCHEMISTRY (2023)

Review Biochemistry & Molecular Biology

Substrate-selective small-molecule modulators of enzymes: Mechanisms and opportunities

Hening Lin

Summary: Small-molecule inhibitors of enzymes are widely used in reverse chemical genetics to explore biology and therapeutic opportunities. However, they may not produce the same phenotype as genetic perturbations due to substrate-selective or substrate-dependent effects. This review discusses examples of substrate-selective inhibitors and emphasizes their advantages over biologics, presenting exciting opportunities for chemical biologists and medicinal chemists.

CURRENT OPINION IN CHEMICAL BIOLOGY (2023)

Editorial Material Biochemistry & Molecular Biology

Christopher T. Walsh: A Prolific Scientist, Effective Academic Leader, and Responsive Mentor

Hening Lin

Summary: Dr. Christopher T. Walsh, a giant in enzymology, passed away in January 2023. This summary briefly highlights his numerous accomplishments in research, academic administration, scientific and industry advising, as well as teaching and mentoring of students and postdoctoral fellows. He has left behind a rich legacy that will continue to inspire generations of scientists.

ACS CHEMICAL BIOLOGY (2023)

Article Biochemistry & Molecular Biology

Trapoxin A Analogue as a Selective Nanomolar Inhibitor of HDAC11

Thanh Tu Ho, Changmin Peng, Edward Seto, Hening Lin

Summary: This article reports the development of trapoxin A analogues as potent and selective inhibitors of HDAC11, an enzyme involved in removing long-chain fatty acyl groups from proteins. One of the analogues, TD034, exhibits nanomolar potency in enzymatic assays and inhibits the defatty acylation of a known HDAC11 substrate in cells. The high potency and selectivity of TD034 could lead to the development of HDAC11 inhibitors for various biological and therapeutic applications.

ACS CHEMICAL BIOLOGY (2023)

Article Biochemistry & Molecular Biology

A Fluorescence Polarization Assay for Macrodomains Facilitates the Identification of Potent Inhibitors of the SARS-CoV-2 Macrodomain

Ananya Anmangandla, Sadhan Jana, Kewen Peng, Shamar D. Wallace, Saket R. Bagde, Bryon S. Drown, Jiashu Xu, Paul J. Hergenrother, J. Christopher Fromme, Hening Lin

Summary: Researchers have developed a robust fluorescence polarization assay for various viral and human macrodomains, including SARS-CoV-2 Macro1, using a novel tracer TAMRA-ADPr. The assay identified GS441524 as a highly selective inhibitor of SARS-CoV-2 Macro1 over other macrodomains.

ACS CHEMICAL BIOLOGY (2023)

Article Chemistry, Multidisciplinary

Structural Basis of Sirtuin 6-Catalyzed Nucleosome Deacetylation

Zhipeng A. Wang, Jonathan W. Markert, Samuel D. Whedon, Maheeshi Yapa Abeywardana, Kwangwoon Lee, Hanjie Jiang, Carolay Suarez, Hening Lin, Lucas Farnung, Philip A. Cole

Summary: The reversible acetylation of histone lysine residues is controlled by the action of acetyltransferases and deacetylases (HDACs), which regulate chromatin structure and gene expression. One member of the HDAC family, Sirt6, efficiently deacetylates several histone H3 acetylation sites on nucleosomes. The structure of Sirt6 bound to a nucleosome reveals its extensive interactions with H2A/H2B acidic patch and nucleosomal DNA, providing insights into how HDACs target and regulate chromatin.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2023)

Article Chemistry, Multidisciplinary

A Turn-On Fluorescent Amino Acid Sensor Reveals Chloroquine?s Effect on Cellular Amino Acids via Inhibiting Cathepsin L

Michael R. Smith, Le Zhang, Yizhen Jin, Min Yang, Anusha Bade, Kevin D. Gillis, Sadhan Jana, Ramesh Naidu Bypaneni, Timothy E. Glass, Hening Lin

Summary: Maintaining the balance of amino acids is important for cell survival and dysfunction of nutrient balance can lead to diseases such as diabetes. In this study, a novel fluorescent sensor called NS560 was developed to detect 18 proteogenic amino acids in mammalian cells. By using NS560, amino acid pools were identified in lysosomes, late endosomes, and near the rough endoplasmic reticulum. Furthermore, the study revealed that Cathepsin L (CTSL) is the target of chloroquine, leading to the accumulation of amino acids in large cellular foci.

ACS CENTRAL SCIENCE (2023)

No Data Available