Phosphorylation/de-phosphorylation in specific sites of tumor suppressor WWOX and control of distinct biological events

Shenq Shyang Huang, Nan-Shan Chang

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

Abnormal differentiation and growth of hematopoietic stem cells cause the development of hematopoietic diseases and hematopoietic malignancies. However, the molecular events underlying leukemia development are not well understood. In our recent study, we have demonstrated that calcium ionophore and phorbol ester force the differentiation of T lymphoblastic leukemia. The event involves a newly identified IκBα/WWOX/ERK signaling, in which WWOX is Ser14 phosphorylated. Additional evidence also reveals that pS14-WWOX is involved in enhancing cancer progression and metastasis and facilitating neurodegeneration. In this mini-review, we update the current knowledge for the functional roles of WWOX under physiological and pathological settings, and provide new insights regarding pS14-WWOX in T leukemia cell maturation, and switching the anticancer pY33-WWOX to pS14-WWOX for cancer promotion and disease progression. Impact statement: WWOX was originally designated as a tumor suppressor. However, human newborns deficient in WWOX do not spontaneously develop tumors. Activated WWOX with Tyr33 phosphorylation is present in normal tissues and organs. However, when pY33-WWOX is overly induced under stress conditions, it becomes apoptotic to eliminate damaged cells. Notably, WWOX with Ser14 phosphorylation is upregulated in the lesions of cancer, as well as in the brain hippocampus and cortex with Alzheimer’s disease. Suppression of pS14-WWOX by Zfra reduces cancer growth and mitigates Alzheimer’s disease progression, suggesting that pS14-WWOX facilitates disease progression. pS14-WWOX can be regarded as a marker of disease progression.

Original languageEnglish
Pages (from-to)137-147
Number of pages11
JournalExperimental Biology and Medicine
Volume243
Issue number2
DOIs
Publication statusPublished - 2018 Jan 1

Fingerprint

Phosphorylation
Tumors
Disease Progression
Neoplasms
Alzheimer Disease
T-Cell Leukemia
Calcium Ionophores
Phorbol Esters
Hematologic Neoplasms
Growth
Hematopoietic Stem Cells
Stem cells
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hippocampus
Brain
Leukemia
Tissue
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

@article{ef04704c5d634b058eec77186ade3858,
title = "Phosphorylation/de-phosphorylation in specific sites of tumor suppressor WWOX and control of distinct biological events",
abstract = "Abnormal differentiation and growth of hematopoietic stem cells cause the development of hematopoietic diseases and hematopoietic malignancies. However, the molecular events underlying leukemia development are not well understood. In our recent study, we have demonstrated that calcium ionophore and phorbol ester force the differentiation of T lymphoblastic leukemia. The event involves a newly identified IκBα/WWOX/ERK signaling, in which WWOX is Ser14 phosphorylated. Additional evidence also reveals that pS14-WWOX is involved in enhancing cancer progression and metastasis and facilitating neurodegeneration. In this mini-review, we update the current knowledge for the functional roles of WWOX under physiological and pathological settings, and provide new insights regarding pS14-WWOX in T leukemia cell maturation, and switching the anticancer pY33-WWOX to pS14-WWOX for cancer promotion and disease progression. Impact statement: WWOX was originally designated as a tumor suppressor. However, human newborns deficient in WWOX do not spontaneously develop tumors. Activated WWOX with Tyr33 phosphorylation is present in normal tissues and organs. However, when pY33-WWOX is overly induced under stress conditions, it becomes apoptotic to eliminate damaged cells. Notably, WWOX with Ser14 phosphorylation is upregulated in the lesions of cancer, as well as in the brain hippocampus and cortex with Alzheimer’s disease. Suppression of pS14-WWOX by Zfra reduces cancer growth and mitigates Alzheimer’s disease progression, suggesting that pS14-WWOX facilitates disease progression. pS14-WWOX can be regarded as a marker of disease progression.",
author = "Huang, {Shenq Shyang} and Nan-Shan Chang",
year = "2018",
month = "1",
day = "1",
doi = "10.1177/1535370217752350",
language = "English",
volume = "243",
pages = "137--147",
journal = "Experimental Biology and Medicine",
issn = "1535-3702",
publisher = "SAGE Publications Ltd",
number = "2",

}

Phosphorylation/de-phosphorylation in specific sites of tumor suppressor WWOX and control of distinct biological events. / Huang, Shenq Shyang; Chang, Nan-Shan.

In: Experimental Biology and Medicine, Vol. 243, No. 2, 01.01.2018, p. 137-147.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Phosphorylation/de-phosphorylation in specific sites of tumor suppressor WWOX and control of distinct biological events

AU - Huang, Shenq Shyang

AU - Chang, Nan-Shan

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Abnormal differentiation and growth of hematopoietic stem cells cause the development of hematopoietic diseases and hematopoietic malignancies. However, the molecular events underlying leukemia development are not well understood. In our recent study, we have demonstrated that calcium ionophore and phorbol ester force the differentiation of T lymphoblastic leukemia. The event involves a newly identified IκBα/WWOX/ERK signaling, in which WWOX is Ser14 phosphorylated. Additional evidence also reveals that pS14-WWOX is involved in enhancing cancer progression and metastasis and facilitating neurodegeneration. In this mini-review, we update the current knowledge for the functional roles of WWOX under physiological and pathological settings, and provide new insights regarding pS14-WWOX in T leukemia cell maturation, and switching the anticancer pY33-WWOX to pS14-WWOX for cancer promotion and disease progression. Impact statement: WWOX was originally designated as a tumor suppressor. However, human newborns deficient in WWOX do not spontaneously develop tumors. Activated WWOX with Tyr33 phosphorylation is present in normal tissues and organs. However, when pY33-WWOX is overly induced under stress conditions, it becomes apoptotic to eliminate damaged cells. Notably, WWOX with Ser14 phosphorylation is upregulated in the lesions of cancer, as well as in the brain hippocampus and cortex with Alzheimer’s disease. Suppression of pS14-WWOX by Zfra reduces cancer growth and mitigates Alzheimer’s disease progression, suggesting that pS14-WWOX facilitates disease progression. pS14-WWOX can be regarded as a marker of disease progression.

AB - Abnormal differentiation and growth of hematopoietic stem cells cause the development of hematopoietic diseases and hematopoietic malignancies. However, the molecular events underlying leukemia development are not well understood. In our recent study, we have demonstrated that calcium ionophore and phorbol ester force the differentiation of T lymphoblastic leukemia. The event involves a newly identified IκBα/WWOX/ERK signaling, in which WWOX is Ser14 phosphorylated. Additional evidence also reveals that pS14-WWOX is involved in enhancing cancer progression and metastasis and facilitating neurodegeneration. In this mini-review, we update the current knowledge for the functional roles of WWOX under physiological and pathological settings, and provide new insights regarding pS14-WWOX in T leukemia cell maturation, and switching the anticancer pY33-WWOX to pS14-WWOX for cancer promotion and disease progression. Impact statement: WWOX was originally designated as a tumor suppressor. However, human newborns deficient in WWOX do not spontaneously develop tumors. Activated WWOX with Tyr33 phosphorylation is present in normal tissues and organs. However, when pY33-WWOX is overly induced under stress conditions, it becomes apoptotic to eliminate damaged cells. Notably, WWOX with Ser14 phosphorylation is upregulated in the lesions of cancer, as well as in the brain hippocampus and cortex with Alzheimer’s disease. Suppression of pS14-WWOX by Zfra reduces cancer growth and mitigates Alzheimer’s disease progression, suggesting that pS14-WWOX facilitates disease progression. pS14-WWOX can be regarded as a marker of disease progression.

UR - http://www.scopus.com/inward/record.url?scp=85040836592&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040836592&partnerID=8YFLogxK

U2 - 10.1177/1535370217752350

DO - 10.1177/1535370217752350

M3 - Review article

VL - 243

SP - 137

EP - 147

JO - Experimental Biology and Medicine

JF - Experimental Biology and Medicine

SN - 1535-3702

IS - 2

ER -