Sains Malaysiana 52(3)(2023):
1273-1289
http://doi.org/10.17576/jsm-2023-5203-18
Emerging Role of SMYD
Family of Proteins in Human Tumorigenesis
(Kemunculan Peranan
Famili SMYD Protein dalam Tumorigenesis Manusia)
AFSHAN BIBI†, AYESHA SARFRAZ†,
AMNA SAJJAD*, IQRA SARFRAZ, AASMA MUNAWWAR, ANEEQA ZARBAB, MEHRAN SATTAR & AZHAR RASUL
Department of Zoology, Faculty of Life Sciences,
Government College University, Faisalabad, 38000 Pakistan
Received: 4 April 2022/Accepted: 7
February 2023
†Theses authors contributed equally to this
work
Abstract
Protein lysine methylation is a
post-translational modification (PTM) that promotes protein complex formation
to regulate DNA replication, gene expression, and repair mechanisms. The Su(Var)3–9, Enhancer-of-zeste and Trithorax (SET) and Myeloid, Nervy, and DEAF-1 (MYND)
domain-containing proteins SMYD are lysine methyltransferases that catalyze the methylation of various histone and non-histone proteins.
There are five members of this SMYD family, and all of these have conserved SET
and MYND domains. The SET domain is divided into two segments by the MYND
domain (the S-sequence and a core SET domain). SMYD Family performs a key role
in numerous biological functions, including growth, development, apoptosis, and
proliferation. SMYD family members are associated with skeletal and cardiac
muscle physiology and pathology. Several studies have shown that aberrant
lysine methylation plays a significant role in oncogenesis.
Recently, the SMYD family has gained importance for its role in various
mechanisms involved in cancer development and progressions, such as methylation
and modification of tumor suppressor proteins (p53 and pRb),
transcriptional factors (STAT3, NF-κB), nuclear
proteins (PARP1), chaperons (Hsp90), protein kinases (MAPK, ERK), and cell
cycle regulatory proteins (CDKN2). SMYD family proteins drive oncogenesis, lead the way to metastasis, and develop chemoresistance, allowing cancer cells to grow, invade the
neighboring tissues, and resist therapeutics. In this review, we summarize SMYD
family members' role in different cancers by focusing on their histone and
non-histone methylation targets and illustrating the mechanism of SMYD
family-mediated oncogenesis.
Keywords: Cancer; chemoresistance; oncogenesis;
SMYD family; tumor suppressor proteins
Abstrak
Pemetilan
protein lisin ialah pengubahsuaian pasca translasi (PTM) yang menggalakkan
pembentukan kompleks protein untuk mengawal selia replikasi DNA, pengekspresan
gen dan mekanisme pembaikan. Protein
yang mengandungi domain Su(Var)3–9, Enhancer-of-zeste dan Trithorax (SET) dan
Myeloid, Nervy dan DEAF-1 (MYND) ialah lisin metiltransferase yang memangkinkan
pemetilan pelbagai protein histon dan bukan histon. Terdapat
lima ahli famili SMYD ini dan kesemua mereka telah memulihara domain SET dan
MYND. Domain SET dibahagikan kepada dua
segmen oleh domain MYND (jujukan S dan domain SET teras). Famili
SMYD melaksanakan peranan penting dalam pelbagai fungsi biologi, termasuk
pertumbuhan, perkembangan, apoptosis dan percambahan. Ahli
famili SMYD dikaitkan dengan fisiologi dan patologi otot rangka dan jantung. Beberapa
kajian telah menunjukkan bahawa pemetilan lisin yang menyimpang memainkan
peranan penting dalam onkogenesis. Baru-baru
ini, famili SMYD telah mendapat kepentingan untuk peranannya dalam pelbagai
mekanisme yang terlibat dalam perkembangan dan janjangan kanser, seperti
pemetilan dan pengubahsuaian protein penindas tumor (p53 dan pRb), faktor
transkrip (STAT3, NF-κB), protein nuklear (PARP1)), chaperon (Hsp90), kinase
protein (MAPK, ERK) dan protein pengawalseliaan kitaran sel (CDKN2). Protein
famili SMYD memacu onkogenesis, membawa kepada metastasis dan membangunkan
rintangan kimia, membolehkan sel kanser berkembang, menyerang tisu jiran dan
menentang terapeutik. Dalam
ulasan ini, kami meringkaskan peranan ahli famili SMYD dalam kanser yang
berbeza dengan memfokuskan pada sasaran pemetilan histon dan bukan histon dan
menggambarkan mekanisme onkogenesis pengantara famili SMYD.
Kata
kunci: Famili SMYD; kanser; kemoterapi; onkogenesis; protein penindas tumor
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*Corresponding author; email: amnasajjad7@yahoo.com
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