Electronic Theses and Dissertations

Date

2024

Document Type

Thesis

Degree Name

Master of Science

Department

Biology

Committee Chair

Amy Abell

Committee Member

Judith A Cole

Committee Member

Omar Skalli

Abstract

Mitogen-activated protein kinase kinase kinase 4 (MAP3K4) promotes fetal and placental growth by regulating growth-promoting pathways. Mice lacking MAP3K4 kinase activity exhibit placental insufficiency and fetal growth restriction. Upstream pathways activating MAP3K4 may represent key mechanisms to induce growth. We have previously shown that the MAP3K4 binding partner tumor necrosis factor receptor-associated factor 4 (TRAF4) promotes MAP3K4 activity in the embryo. However, the role of TRAF4 and its association with MAP3K4 in the placenta is unknown. Our analysis of single-cell RNA-Seq data showed that Traf4 is one of the most abundant Trafs in the mouse placenta and is coexpressed with Map3k4 in trophoblast stem (TS) cells and placental labyrinth progenitors. MAP3K4 kinase inactivation in TS cells leads to increased TRAF4 expression relative to WT TS cells, suggesting a possible compensatory mechanism. Our previous work showing MAP3K4-dependent control of CREB-binding protein (CBP) and histone deacetylase 6 (HDAC6) prompted us to examine the impact of CBP and HDAC6 on Traf4. Though we saw no effect of CBP or HDAC6 on Traf4 transcript, we observed HDAC6-dependent effects on TRAF4 protein. HDAC6 promoted TRAF4 expression by binding the TRAF4 TRAF domain and stabilizing TRAF4 independent of HDAC6 deacetylase activity. Together, our findings identify a previously unknown interaction of HDAC6 with TRAF4 that promotes TRAF4 expression.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest.

Notes

Embargoed until 07-02-2026

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Available for download on Thursday, July 02, 2026

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