BIRC7

BIRC7 Full Name

baculoviral IAP repeat containing 7

BIRC7 Introduction

BIRC7 encodes a member of the inhibitor of apoptosis (IAP) protein family, best known by the aliases Livin and melanoma inhibitor of apoptosis (ML-IAP). The gene resides on chromosome 20q13.33 and was independently discovered as both Livin and KIAP (kidney inhibitor of apoptosis protein), a dual naming history that reflects its initial identification in melanoma and renal contexts. The protein contains a single baculoviral IAP repeat (BIR) domain together with a C-terminal RING-type zinc finger, a minimal architecture that distinguishes it from the multi-BIR IAPs such as XIAP. The BIR domain binds and inhibits active caspases, while the RING domain confers E3 ubiquitin ligase activity, allowing BIRC7 to tag pro-apoptotic proteins such as the caspase activator SMAC/DIABLO for proteasomal degradation. Two alternatively spliced isoforms, Livin alpha and Livin beta, differ in their C-terminal tails and show distinct anti-apoptotic potencies in response to different death stimuli. Because its expression is largely absent from most adult tissues but reappears in many malignancies, BIRC7 is viewed as a tumor-associated survival factor whose overabundance can blunt chemotherapy-induced apoptosis.

Figure 1. Structure of BIRC7 and its variants. (Source: Dhiego Botelho Rigato, et al. 2019)

Beyond its core caspase-inhibitory role, BIRC7 participates in several signaling circuits that reinforce cell survival. It can engage the TAK1/JNK pathway and modulate nuclear factor-kappaB signaling, and it is subject to regulation by lineage-specific transcription factors, including microphthalmia-associated transcription factor in melanoma. Elevated BIRC7 levels have been documented across a wide range of tumors such as melanoma, breast, prostate, lung, and hematological malignancies, where they correlate with aggressiveness and resistance to therapy. Experimental suppression of BIRC7 in tumor models restores apoptotic sensitivity and restrains growth, supporting its appeal as a therapeutic target. Small-molecule IAP antagonists designed to neutralize BIR domains and trigger degradation of cIAPs and BIRC7 are under investigation as a strategy to disarm the apoptosis blockade in cancer cells. The combination of restricted normal-tissue expression and potent anti-death activity makes BIRC7 a compelling yet challenging node for selective anticancer intervention.

Alternate Names for BIRC7

BIRC7; baculoviral IAP repeat containing 7; KIAP; LIVIN; MLIAP; RNF50; ML-IAP; baculoviral IAP repeat-containing protein 7; RING finger protein 50; livin inhibitor of apoptosis; kidney inhibitor of apoptosis protein; melanoma inhibitor of apoptosis protein;

• 1. Dhiego Botelho Rigato, et al. BIRC7 (baculoviral IAP repeat containing 7). Atlas Genet Cytogenet Oncol Haematol. 2019-09-01.
  2. Abd-Elrahman I, et al. The inhibitor of apoptosis protein Livin (ML-IAP) plays a dual role in tumorigenicity. Cancer Res. 2009 Jul 1;69(13):5475-80.