MACROD2

Last update 08 May 2025

Basic Info

Synonyms

[Protein ADP-ribosylaspartate] hydrolase MACROD2, [Protein ADP-ribosylglutamate] hydrolase MACROD2, ADP-ribose glycohydrolase MACROD2

+ [6]

Introduction

Removes ADP-ribose from aspartate and glutamate residues in proteins bearing a single ADP-ribose moiety (PubMed:23474712, PubMed:23474714). Inactive towards proteins bearing poly-ADP-ribose (PubMed:23474712, PubMed:23474714). Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins (PubMed:21257746).

100 Clinical Results associated with MACROD2

100 Translational Medicine associated with MACROD2

0 Patents (Medical) associated with MACROD2

132

Literatures (Medical) associated with MACROD2

01 Jan 2025·Oral Oncology

Letter to the editor, “Loss of MACROD2 drives radioresistance but not cisplatin resistance in HPV-positive head and neck cancer.”

Letter

Author: Jeyaraj, Gnanaprakash

01 Dec 2024·Oral Oncology

Loss of MACROD2 drives radioresistance but not cisplatin resistance in HPV-positive head and neck cancer

Article

Author: Nichols, Anthony C. ; Karimi, Amir Hossein ; Palma, David A. ; Barrett, John W ; Khan, Halema ; Ryan, Sarah E.B. ; Dawson, Alice ; Gazala, Walid ; Shaikh, Mushfiq H ; Mendez, Adrian ; Ryan, Sarah E B ; Cecchini, Matthew ; Shaikh, Mushfiq H. ; Zeng, Peter Y.F. ; Pan, Harrison ; Mymryk, Joe S ; Mymryk, Joe S. ; Zeng, Peter Y F ; Palma, David A ; Barrett, John W. ; Nichols, Anthony C

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type worldwide. In recent years, there has been an increase in the rate of HNSCC cases attributed to the infection of the oropharynx by the human papillomavirus (HPV). Given the significant treatment-related toxicities of the current standard of care for HPV-positive HNSCC, there is an urgent need for the development of precision patient stratification and treatment strategies to improve patients' quality of life while maintaining excellent survival rates. We have previously carried out whole genome sequencing of HPV+ HNSCC tumors that failed concurrent cisplatin and radiation treatment and discovered that MACROD2 deletion is enriched among these tumors. In the current study, we sought to investigate the mechanistic role of MACROD2 in HPV+ HNSCC treatment resistance. Our results indicate that MACROD2 depletion in HNSCC cell lines leads to increased cell viability and colony formation capacity. Interestingly, MACROD2 depletion did not alter cisplatin sensitivity but led to an increase in radiation resistance of HPV+ HNSCC cell lines. RNA sequencing and immunofluorescence microscopy demonstrated that MACROD2-depleted HPV+ HNSCC cells displayed elevated levels of hypoxia and an altered DNA damage response. Taken together, this study establishes and characterizes the role of MACROD2 in HPV+ HNSCC radioresistance. Further work is needed to validate MACROD2 as a biomarker of treatment failure and to understand how to overcome the identified molecular mechanisms of resistance.

01 Dec 2024·The Journal of Molecular Diagnostics

High Prevalence of Chromosomal Rearrangements and LINE Retrotranspositions Detected in Formalin-Fixed, Paraffin-Embedded Colorectal Cancer Tissue

Article

Author: van den Broek, Daan ; van Bree, Elisabeth J. ; Meijer, Gerrit A. ; Vessies, Daan C L ; Delis-van Diemen, Pien ; Rubio-Alarcón, Carmen ; Heringa, Jaap ; van ‘t Erve, Iris ; Mekkes, Nienke J. ; Meijer, Gerrit A ; van Bree, Elisabeth J ; Feitsma, Harma ; Punt, Cornelis J A ; Linders, Theodora ; Abeln, Sanne ; Mekkes, Nienke J ; Fijneman, Remond J.A. ; Diemen, Pien Delis-van ; Vessies, Daan C.L. ; Lakbir, Soufyan ; van 't Erve, Iris ; Swennenhuis, Joost ; Fijneman, Remond J A ; Tijssen, Marianne ; Lanfermeijer, Mirthe ; Stelloo, Ellen ; Punt, Cornelis J.A.

Structural variants (SVs) caused by chromosomal rearrangements in common fragile sites or long interspersed nuclear element (LINE) retrotranspositions are highly prevalent in colorectal cancer. However, methodology for the targeted detection of these SVs is lacking. This article reports the use of formalin-fixed, paraffin-embedded targeted-locus capture (FFPE-TLC) sequencing as a novel technology for the targeted detection of tumor-specific SVs. Analysis of 29 FFPE colorectal tumor samples and 8 matched normal samples revealed tumor-specific SVs in 24 patients (83%), with a median of 2 SVs per patient (range, 1 to 21). A total of 104 SVs were found in the common fragile site-associated genes MACROD2, PRKN, FHIT, and WWOX in 18 patients (62%), and 39 SVs caused by three LINE transposable elements were found in 15 patients (52%). Tumor specificity of SVs was independently verified by droplet digital PCR of tumor tissue DNA, and their applicability as plasma circulating tumor DNA biomarkers was demonstrated. FFPE-TLC sequencing enabled the detection of tumor-specific SVs caused by chromosomal rearrangements and LINE retrotranspositions in FFPE tissue. Therefore, FFPE-TLC sequencing facilitates the investigation of the biological and clinical effects of SVs using FFPE material from (retrospective) cohorts of cancer patients and has potential clinical applicability in the detection of SV biomarkers in the routine molecular diagnostics setting.

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MACROD2

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