Acute Myeloid Leukemia-Related Proteins Modified by Ubiquitin and Ubiquitin-like Proteins

Abstract

Acute myeloid leukemia (AML), the most common form of an acute leukemia, is a malignant disorder of stem cell precursors of the myeloid lineage. Ubiquitination is one of the post-translational modifications (PTMs), and the ubiquitin-like proteins (Ubls; SUMO, NEDD8, and ISG15) play a critical role in various cellular processes, including autophagy, cell-cycle control, DNA repair, signal transduction, and transcription. Also, the importance of Ubls in AML is increasing, with the growing research defining the effect of Ubls in AML. Numerous studies have actively reported that AML-related mutated proteins are linked to Ub and Ubls. The current review discusses the roles of proteins associated with protein ubiquitination, modifications by Ubls in AML, and substrates that can be applied for therapeutic targets in AML.

<I>GATA3</I> rs3824662<i>, IKZF1</i> (rs4132601& rs11978267), and <I>ARID5B</I> (rs10821936 & rs10994982) Gene Polymorphisms in Egyptian Adult Patients with Acute Leukemia

“…The prevalence of ALL shows variation in different populations [5] and several genetic SNPs in many genes (such as ARID5B, CEBPE, GATA3 and IKZF1) have been linked to the susceptibility and poor outcome in pediatric ALL [7,18,20,21,[27][28][29]. AML is the most common form of acute leukemia in adults and is characterized by clonal expansion of myeloblasts with heterogeneous genetic and epigenetic alterations [8,30,31].…”

N6-methyladenosine-modified SENP1, identified by IGF2BP3, is a novel molecular marker in acute myeloid leukemia and aggravates progression by activating AKT signal via de-SUMOylating HDAC2

“…AML is caused by gene mutations, chromatin abnormalities, and protein conformational changes that shift the growth and differentiation of hematopoietic stem cells [2]. In recent decades, a number of post-translational modifications of proteins (such as ubiquitination or small ubiquitin-like modifiers) have been reported to play a significant role in AML [3]. Previously, we reported some genetic mechanisms of AML, such as m6A modification and alternative splicing [4].…”

Almost 50 Years of Monomeric Extracellular Ubiquitin (eUb)

“…In addition to Ub, other small ubiquitin-like (UBL) proteins are found in eukaryotic cells, including NEDD8, UFM1, ISG15, ATG8, URM1, SAP1, SUMO, and FAT10 [ 9 ]. Some UBLs have also been described in prokaryotes, such as the Mycobacterium tuberculosis prokaryotic-ubiquitin-like-protein (Pup).…”