Rhomboid domain containing 1 inhibits cell apoptosis by upregulating AP-1 activity and its downstream target Bcl-3

• RHBDD1 could induce the specific activation of AP-1 in a dose-dependent manner.
• RHBDD1 overexpression increased c-Jun activity, and the activity was visibly inhibited when RHBDD1 was knocked down.
• RHBDD1 functioned as an antiapoptotic protein by regulating Bcl-3, which is the downstream target of AP-1.

We have previously reported that rhomboid domain containing 1 (RHBDD1), a new member of the Rhomboid family, is highly expressed in testis. In the present work, luciferase analyses showed that RHBDD1 enhanced the AP-1 activity in a dose- and activity-dependent manner. RHBDD1 overexpression increased c-Jun activity, and the activity was visibly inhibited when RHBDD1 was knocked down. The suppression of c-Jun by inactivation of RHBDD1 was rescued by overexpressing RHBDD1. However, c-Jun overexpression did not alter the expression level of RHBDD1. Furthermore, knockdown of RHBDD1 led to increased cell apoptosis and reduced expression of Bcl-3. Our findings indicate that RHBDD1 could inhibit cell apoptosis by activating and upregulating c-Jun and its downstream target, Bcl-3.